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Background and Objectives: Collateral status is a pivotal determinant of clinical outcomes in acute ischemic stroke (AIS); however, its evaluation can be challenging. We investigated the predictive value of CT perfusion (CTP) derived time and density alterations versus CTP for collateral status prediction in AIS., Methods: Consecutive patients with anterior circulation occlusion within 24 h were retrospectively included. Time-density curves of the CTP specified ischemic core, penumbra, and the corresponding contralateral unaffected brain were obtained. The collateral status was dichotomised into robust (4-5 scores) and poor (0-3 scores) using multiphase collateral scoring, as described by Menon et al.. Receiver operating characteristic curves and multivariable regression analysis were performed to assess the predictive ability of CTP-designated tissue time and density alterations, CTP for robust collaterals, and favourable outcomes (mRS score of 0-2 at 90 days)., Results: One-hundred patients (median age, 68 years; interquartile range, 57-80 years; 61 men) were included. A smaller ischemic core, shorter peak time delay, lower peak density decrease, lower cerebral blood volume ratio, and cerebral blood flow ratio in the CTP specified ischemic core were significantly associated with robust collaterals (P FDR  ≤ 0.004). The peak time delay demonstrated the highest diagnostic value (AUC, 0.74; P < 0.001) with 66.7 % sensitivity and 73.7 % specificity. Furthermore, the peak time delay of less than 8.5 s was an independent predictor of robust collaterals and favourable clinical outcomes., Conclusions: Robust collateral status was significantly associated with the peak time delay in the ischemic core. It is a promising image marker for predicting collateral status and functional outcomes in AIS., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Two undescribed cladosporol derivatives, cladosporols J-K (1-2), and three previously unreported spirobisnaphthalenes, urnucratins D-F (3-5), as well as eleven known cladosporols (6-16), were characterized from Cladosporium cladosporioides (Cladosporiaceae), a common plant pathogen isolated from the skin of Chinese toad. Cladosporols J-K (1-2) with a single double bond have been rarely reported, while urnucratins D-F (3-5) featured an unusual benzoquinone bisnaphthospiroether skeleton, contributing to an expanding category of undiscovered natural products. Their structures and absolute configurations were determined using extensive spectroscopic methods, including NMR, HRESIMS analyses, X-ray single crystal diffraction, as well as through experimental ECD analyses. Biological assays revealed that compounds 1 and 2 exhibited inhibitory activity against A549 cells, with IC 50 values of 30.11 ± 3.29 and 34.32 ± 2.66 μM, respectively., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Lidocaine is the most frequently applied local infiltration anesthetic agent for treating tendinopathies. However, studies have discovered lidocaine to negatively affect tendon healing. In the current study, the molecular mechanisms and effects of lidocaine on tenocyte migration were evaluated. We treated tenocytes intrinsic to the Achilles tendons of Sprague-Dawley rats with lidocaine. The migration ability of cells was analyzed using electric cell-substrate impedance sensing (ECIS) and scratch wound assay. We then used a microscope to evaluate the cell spread. We assessed filamentous actin (F-actin) cytoskeleton formation through immunofluorescence staining. In addition, we used Western blot analysis to analyze the expression of phospho-focal adhesion kinase (FAK), FAK, phospho-paxillin, paxillin, and F-actin. We discovered that lidocaine had an inhibitory effect on the migration of tenocytes in the scratch wound assay and on the ECIS chip. Lidocaine treatment suppressed cell spreading and changed the cell morphology and F-actin distribution. Lidocaine reduced F-actin formation in the tenocyte during cell spreading; furthermore, it inhibited phospho-FAK, F-actin, and phospho-paxillin expression in the tenocytes. Our study revealed that lidocaine inhibits the spread and migration of tenocytes. The molecular mechanism potentially underlying this effect is downregulation of F-actin, phospho-FAK, and phospho-paxillin expression when cells are treated with lidocaine., (© 2023 Orthopaedic Research Society.)

Xanthone-chromanone homo- or heterodimers are regarded as a novel class of topoisomerase (Topo) inhibitors; however, limited information about these compounds is currently available. Here, 14 new ( 1 - 14 ) and 6 known tetrahydroxanthone chromanone homo- and heterodimers ( 15 - 20 ) are reported as isolated from Penicillium chrysogenum C-7-2-1. Their structures and absolute configurations were unambiguously demonstrated by a combination of spectroscopic data, single-crystal X-ray diffraction, modified Mosher's method, and electronic circular dichroism analyses. Plausible biosynthetic pathways are proposed. For the first time, it was discovered that tetrahydroxanthones can convert to chromanones in water, whereas chromone dimerization does not show this property. Among them, compounds 5 , 7 , 8 , and 16 exhibited significant cytotoxicity against H23 cell line with IC 50 values of 6.9, 6.4, 3.9, and 2.6 μM, respectively.

Diabetic cardiomyopathy (DCM) is a serious complication of type 2 diabetes mellitus (T2DM) that contributes to cardiovascular morbidity and mortality. However, the metabolic alterations and specific biomarkers associated with DCM in T2DM remain unclear. In this study, we conducted a comprehensive metabolomic analysis using liquid chromatography-mass spectrometry (LC-MS) to investigate the plasma metabolite profiles of T2DM patients with and without DCM. We identified significant differences in metabolite levels between the groups, highlighting the dysregulation of various metabolic pathways, including starch and sucrose metabolism, steroid hormone biosynthesis, tryptophan metabolism, purine metabolism, and pyrimidine metabolism. Although several metabolites showed altered abundance in DCM, they also shared characteristics of DCM and T2DM rather than specific to DCM. Additionally, through biomarker analyses, we identified potential biomarkers for DCM, such as cytidine triphosphate, 11-ketoetiocholanolone, saccharopine, nervonic acid, and erucic acid. These biomarkers demonstrated distinct patterns and associations with metabolic pathways related to DCM. Our findings provide insights into the metabolic changes associated with DCM in T2DM patients and highlight potential biomarkers for further validation and clinical application. Further research is needed to elucidate the underlying mechanisms and validate the diagnostic and prognostic value of these biomarkers in larger cohorts.

Muscle injuries are common among athletes and often treated with platelet-rich plasma (PRP). However, whether the leukocyte concentration affects the efficacy of PRP in treating muscle injuries remains unclear. This study investigated the effects of leukocyte-poor platelet-rich plasma (LP-PRP) and leukocyte-rich platelet-rich plasma (LR-PRP) on myoblast proliferation and the molecular mechanisms underlying these effects. Myoblasts were treated with 0.5% LP-PRP, 0.5% LR-PRP, 1% LP-PRP, or 1% LR-PRP for 24 h. The gene expression of the LP-PRP- and LR-PRP-treated myoblasts was determined using RNA sequencing analysis. Cell proliferation was evaluated using an bromodeoxyuridine (BrdU) assay, and cell cycle progression was assessed through flow cytometry. The expression of cyclin A, cyclin-dependent kinase 1 (cdk1), and cdk2 was examined using Western blotting. The expression of myoblast determination protein 1 (MyoD1) was examined through Western blotting and immunofluorescence staining. The LP-PRP and LR-PRP both promoted the proliferation of myoblasts and increased differential gene expression of myoblasts. Moreover, the LP-PRP and LR-PRP substantially upregulated the expression of cyclin A, cdk1, and cdk2. MyoD1 expression was induced in the LP-PRP and LR-PRP-treated myoblasts. Our results corroborate the finding that LP-PRP and LR-PRP have similar positive effects on myoblast proliferation and MyoD1 expression., (© 2023 Orthopaedic Research Society.)

Objective: To study the complications of ultrasound-guided radiofrequency ablation (RFA) in chronic kidney disease (CKD) patients undergoing renal replacement therapy with secondary hyperparathyroidism (SHPT)., Methods: This retrospective study reviewed the clinical data, including general information, examination results, treatment times, time interval, and postoperative complications, of 103 SHPT patients who received ultrasound-guided RFA treatment from July 2017 to January 2021., Results: Of 103 patients, 52 required two sessions of RFA within a month. The incidence of recurrent laryngeal nerve injury at the second treatment was significantly higher than that at the first treatment (first session vs. second session, 5.77% vs. 21.15%; p  = .021). Of all the enrolled 103 patients, 27 suffered complications after the first session of RFA. When we separated patients into complications group and non-complication group, we detected more ablated nodules in the complications group ( Z  = -2.222; p  = .0026). Subgroup analysis further showed that the patients in the severe hypocalcemia group were younger ( p  = .005), had more ablated nodules ( p  = .003) and higher blood phosphorus ( p  = .012) and alkaline phosphatase (ALP) levels ( p  = .002). Univariate analysis showed that age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA., Conclusions: An interval of more than 1 month between two treatments may help to avoid recurrent laryngeal nerve injury. Age, serum phosphorus, ALP, and number of ablated nodules were associated with a higher risk of severe hypocalcemia after the first session of RFA.

Lung cancer remains the leading cause of cancer-related death. In addition to chest X-rays and computerised tomography, the detection of cancer biomarkers serves as an emerging diagnostic tool for lung cancer. This review explores biomarkers including the rat sarcoma gene, the tumour protein 53 gene, the epidermal growth factor receptor, the neuron-specific enolase, the cytokeratin-19 fragment 21-1 and carcinoembryonic antigen as potential indicators of lung cancer. Biosensors, which utilise various transduction techniques, present a promising solution for the detection of lung cancer biomarkers. Therefore, this review also explores the working principles and recent implementations of transducers in the detection of lung cancer biomarkers. The transducing techniques explored include optical techniques, electrochemical techniques and mass-based techniques for detecting biomarkers and cancer-related volatile organic compounds. Graphene has outstanding properties in terms of charge transfer, surface area, thermal conductivity and optical characteristics, on top of allowing easy incorporation of other nanomaterials. Exploiting the collective merits of both graphene and biosensor is an emerging trend, as evidenced by the growing number of studies on graphene-based biosensors for the detection of lung cancer biomarkers. This work provides a comprehensive review of these studies, including information on modification schemes, nanomaterials, amplification strategies, real sample applications, and sensor performance. The paper concludes with a discussion of the challenges and future outlook of lung cancer biosensors, including scalable graphene synthesis, multi-biomarker detection, portability, miniaturisation, financial support, and commercialisation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Background: Coronavirus disease 2019 (COVID-19) poses a significant threat to the safety of residents in long-term care facilities, and the staff of long-term care facilities are essential in the care and prevention of major infectious diseases and therefore require good health literacy to ensure the health of residents. The main objective of this study was to examine the health literacy of staff in long-term care facilities and analyze the factors associated with their COVID-19 health literacy in Taiwan to provide a basis for the response mechanism to emerging infectious diseases., Methods: A cross-sectional survey with a structured questionnaire by a convenience sample method and to assess the COVID-19 health literacy of caregivers working in long-term care facilities in this study. The COVID-19 health literacy scale was a self-administered scale designed to combine the concept of "health literacy" with the 3 levels and 5 stages of preventive medicine. A total of 385 workers from 10 long-term care facilities were surveyed as the study sample, and the validated questionnaires were statistically analyzed using SPSS version 22.0 statistical software. A multivariate logistic regression model was used to establish the associated factors of the COVID-19 health literacy level., Results: Overall, the mean COVID-19 health literacy score was 88.7 ± 10.4 (range: 58-105). Using a quartile scale, 92 (23.9%) of the study participants had low health literacy (health literacy score < 82), 190 (49.3%) had average health literacy (health literacy score 82-98), and the remaining 103 (26.8%) had good health literacy (health literacy score 99-105). Statistical analysis revealed significant differences (p < 0.05) in the COVID-19 health literacy score by demographic variables (education, job category, number of daily service users, and training related to infectious disease prevention and control) of the study population. The logistic regression analysis of the COVID-19 health literacy level (> 82 vs. ≤82) showed a significant difference in the study sample by gender (male vs. female, OR = 2.46, 95% CI = 1.15-5.26), job category (nurse practitioner vs. caregiver, OR = 7.25, 95% CI = 2.46-21.44), monthly service hours (> 160 h vs. 40-79 h, OR = 0.044, 95% CI = 0.07-0.97), experience caring for confirmed COVID-19 patients (yes vs. no, OR = 0.13, 95% CI = 0.02-0.98), and training related to infectious disease prevention and control (yes vs. no, OR = 2.8, 95% CI = 1.52-5.15)., Conclusions: This study recommends that facilities provide immediate updated COVID-19 information to staff, especially frontline caregivers, and specifically enhance COVID-19 infection control education training for all facility staff to eliminate health literacy disparities., (© 2023. The Author(s).)

Malignant glioma is the most fatal, invasive brain cancer with limited treatment options. Our previous studies show that 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1), a major metabolite of indole-3-carbinol (I3C) derived from cruciferous vegetables, produces anti-tumour effect against various tumour cell lines. In this study we characterized LTr1 as a novel anti-glioma agent. Based on screening 134 natural compounds and comparing the candidates' efficacy and toxicity, LTr1 was selected as the lead compound. We showed that LTr1 potently inhibited the viability of human glioma cell lines (SHG-44, U87, and U251) with IC 50 values of 1.97, 1.84, and 2.03 μM, respectively. Furthermore, administration of LTr1 (100,300 mg· kg -1  ·d -1 , i.g. for 18 days) dose-dependently suppressed the tumour growth in a U87 xenograft nude mouse model. We demonstrated that LTr1 directly bound with TrkA to inhibit its kinase activity and the downstream PI3K/AKT pathway thus inducing significant S-phase cell cycle arrest and apoptosis in SHG-44 and U87 cells by activating the mitochondrial pathway and inducing the production of reactive oxygen species (ROS). Importantly, LTr1 could cross the blood-brain barrier to achieve the therapeutic concentration in the brain. Taken together, LTr1 is a safe and promising therapeutic agent against glioma through inhibiting TrkA/PI3K/AKT pathway., (© 2022. The Author(s), under exclusive licence to Shanghai Institute of Materia Medica, Chinese Academy of Sciences and Chinese Pharmacological Society.)

Background and Objective: Central nervous system (CNS) infiltration commonly occurs in children with acute lymphoblastic leukemia (ALL). Nevertheless, CNS infiltration is rarely detected at the initial diagnosis. The glymphatic system, which regulates cerebrospinal fluid (CSF) and interstitial fluid transport, is considered one of the possible routes of CNS infiltration by leukemia cells. In this study, we used diffusion tensor image analysis along the perivascular space (DTI-ALPS) method to investigate glymphatic system function and obtained CSF volume using synthetic magnetic resonance imaging (SyMRI) in pediatric ALL without clinically diagnosed CNS infiltration., Materials and Methods: Twenty-nine ALL and 29 typically developing (TD) children were prospectively recruited (age 4-16 years) in the present study. Group differences in brain volumetric parameters, brain water diffusivities, and the ALPS index were evaluated after controlling for age, gender, and handedness. Furthermore, significant group-different parameters were correlated with clinical information using partial correlations analysis., Results: Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all p FDR-corrected  < 0.05). Moreover, the ALPS index was negatively associated with the risk classification (r =  - 0.59, p FDR-corrected  = 0.04) in pediatric ALL., Conclusions: Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration. These novel findings suggested that the glymphatic system might be essential in the early-stage process of ALL CNS infiltration, which provides a new direction for exploring underlying mechanisms and early detection of pediatric ALL CNS infiltration., Key Points: • Lower Dxassoc and ALPS index, and increased CSF volume were found in pediatric ALL (all p FDR-corrected  < 0.05). • The ALPS index was negatively associated with the risk classification (r =  -0.59, p FDR-corrected  = 0.04) in pediatric ALL. • Dysfunction of the glymphatic system and accumulation of CSF were presented in pediatric ALL without clinically diagnosed CNS infiltration, which suggested that the ALPS index and CSF volume might be promising imaging markers for early detection of pediatric ALL CNS infiltration., (© 2023. The Author(s), under exclusive licence to European Society of Radiology.)

The coronavirus disease 2019 (COVID-19) pandemic has exerted tremendous effects on the residents of and caregivers at long-term care facilities (LTCF). The combination of a vulnerable, aged population, staffing shortages, and inadequate resources in LTCF will cause a great negative impact in these sectors. Addressing the caregiver's lack of interest in providing care for patients with COVID-19 is a great challenge for institutional managers. The primary objective of this study was to analyze the factors related to the willingness of personnel at LTCF to provide care to patients with COVID-19. This was a cross-sectional study in which personnel from 10 LTCF were recruited as participants through convenience sampling and completed structured questionnaires. A total of 500 questionnaires were distributed and 385 valid questionnaires were recovered, posting a response rate of 77%. A statistical analysis was performed using SPSS 22.0. The results of the survey revealed that only 30% of the participants were willing to provide care to patients with COVID-19; 23% more of the participants were willing to provide such care if their institutions provided sufficient PPE. Regarding other conditions, 31.5% and 76% of the participants expressed that they would be willing to provide such care if their compensation were increased and working hours were reduced. In the univariate analysis, the willingness of participants with different characteristics (job categories, years of holding a professional certificate, job location type, monthly income, experience with caring for patients with confirmed COVID-19, and completion of training related to communicable disease control) varied significantly ( p < 0.05). Furthermore, in the logistic regression analysis, several demographic and professional characteristics (education level, job category, number of patients served daily, and monthly income) were significantly correlated with willingness to provide care to patients with COVID-19 ( p < 0.05). On the basis of these findings, the LTCF should securitize the associated factors of care wiliness in personnel to eliminate the difference of the willingness to provide care to patients with suspected or confirmed COVID-19.

This study assessed patient satisfaction and its associated factors among male drug-using inmates utilizing a prison detention clinic in Taiwan. A cross-sectional design and structured questionnaire were employed to recruit 580 drug-using inmates into the study. The Patient Satisfaction Questionnaire Short Form (PSQ-18), developed by the RAND Corporation, was used as the basis for the short scale of patient satisfaction, and the research data were analyzed using the SPSS for Windows 20.0 statistical software package. The results showed that the research subjects had low patient satisfaction in all the factors assessed compared with the scale's general norms. Among the original seven satisfaction subscales in this study, the highest score was for the financial aspects, and the lowest was for the amount of time spent with doctors. This study also investigated satisfaction with medical lab exams and the pharmacy at the prison's clinic, and the satisfaction scores were higher than the original seven subscales. In multiple logistic regression analyses, the final model indicated that the inmates undergoing observed rehabilitation (OR = 13.837, 95% CI = 2.736-69.983) were more likely satisfied with prison detention clinic c than those serving prison sentences. Those inmates with custodial deposits (high vs. low; OR = 1.813, 95% CI = 1.038-3.168), and meet their physical health needs (met vs. unmet; OR = 4.872, 95% CI = 2.054-11.560) had significant correlated with detention clinic care satisfactory level. Although there is only one study setting cannot give a generalizability for people who are incarcerated in Taiwan, this study highlights that the prison authorities should scrutinize factors associated with detention clinic care satisfaction, such as the type of inmate, economic status in the prison, self-reported health status, and their physical health needs, to increase the level of patient satisfaction., (© 2022. The Author(s).)

Lidocaine injection is a common treatment for tendon injuries. However, the evidence suggests that lidocaine is toxic to tendon cells. This study investigated the effects of lidocaine on cultured tendon cells, focusing on the molecular mechanisms underlying cell proliferation and extracellular matrix (ECM) production. Tendon cells cultured from rat Achilles tendons were treated with 0.5, 1.0, or 1.5 mg/mL lidocaine for 24 h. Cell proliferation was evaluated by Cell Counting Kit 8 (CCK-8) assay and bromodeoxyuridine (BrdU) assay. Cell apoptosis was assessed by Annexin V and propidium iodide (PI) stain. Cell cycle progression and cell mitosis were assessed through flow cytometry and immunofluorescence staining, respectively. The expression of cyclin E, cyclin A, cyclin-dependent kinase 2 (CDK2), p21, p27, p53, matrix metalloproteinases-2 (MMP-2), matrix metalloproteinases-9 (MMP-9), type I collagen, and type III collagen were examined through Western blotting, and the enzymatic activity of MMP-9 was determined through gelatin zymography. Lidocaine reduced cell proliferation and reduced G1/S transition and cell mitosis. Lidocaine did not have a significant negative effect on cell apoptosis. Lidocaine significantly inhibited cyclin A and CDK2 expression but promoted p21, p27, and p53 expression. Furthermore, the expression of MMP-2 and MMP-9 increased, whereas that of type I and type III collagen decreased. Lidocaine also increased the enzymatic activity of MMP-9. Our findings support the premise that lidocaine inhibits tendon cell proliferation by changing the expression of cell-cycle-related proteins and reduces ECM production by altering levels of MMPs and collagens.

Effect of external-recycle operations on the heat-transfer efficiency, specifically for the power-law fluid flowing in double-pass concentric circular heat exchanger under sinusoidal wall fluxes, is investigated theoretically in the developed countries. Given that the fluid is heated twice on both sides of the impermeable sheet, four flow patterns proposed in recycling double-pass operations are expected to make substantial improvements in the performance of heat exchanger device in this study. Theoretical predictions point out that the heat-transfer efficiency increases with the ratio of channel thickness of double-pass concentric circular heat exchanger for all new designs under the same working dimension and the operational condition. The fluid velocity within the double-pass heat exchanger is increased by the fluids flowing through divided subchannels, which contributed to the higher convective heat-transfer efficiency. A simplified mathematical formulation was derived for double-pass concentric circular heat exchangers and would be a significant contribution to analyze heat transfer problems with sinusoidal wall fluxes at boundaries. The results deliver the optimal performance for the proposed four configurations with the use of external recycle compared to those conducted in single-pass, where an impermeable sheet is not inserted. The influences of power-law index and impermeable-sheet position on average Nusselt numbers under various flow patterns are also delineated. The distribution of dimensionless wall temperature was lower at the level of relative smaller thickness of annular channel, and the average Nusselt numbers for four external-recycle configurations and single-pass device were more suitable for operating under same condition. The ratio of the power consumption increment to heat-transfer efficiency enhancement demonstrates the economic feasibility among various configurations of double-pass concentric circular heat exchanger. The results also show that the external-recycle configuration (say Type B in the present study) serves as an important economic advantage in designing concentric circular heat exchangers for heating power-law fluids due to the smaller volumetric flow rate in annular channel with exiting outlet temperature.

A plenty of cytochrome P450s have been annotated in the Daldinia eschosholzii genome. Inspired by the fact that some P450s have been reported to catalyze the carbon-nitrogen (C-N) bond formation, we were curious about whether hybrids through C-N bond formation could be generated in the indole-3-carbinol (I3C) exposed culture of D. eschscholzii . As expected, two skeletally undescribed polyketide-indole hybrids, designated as indolpolyketone A and B ( 1 and 2 ), were isolated and assigned to be constructed through C-N bond formation. Their structures were elucidated by 1D and 2D NMR spectra. The absolute configurations of 1 and 2 were determined by comparing the recorded and calculated electronic circular dichroism (ECD) spectra. Furthermore, the plausible biosynthetic pathways for 1 and 2 were proposed. Compounds 1 and 2 exhibited significant antiviral activity against H1N1 with IC 50 values of 45.2 and 31.4 μM, respectively. In brief, compounds 1 and 2 were reported here for the first time and were the first example of polyketide-indole hybrids pieced together through C-N bond formation in the I3C-exposed culture of D. eschscholzii . Therefore, this study expands the knowledge about the chemical production of D. eschscholzii through precursor-directed biosynthesis (PDB)., Competing Interests: The authors declare that they have no conflicts of interest., (© 2022 The Authors.)

Statins are the most effective therapeutic agents for reducing cholesterol synthesis. Given their widespread use, many adverse effects from statins have been reported; of these, musculoskeletal complications occurred in 15% of patients after receiving statins for 6 months, and simvastatin was the most commonly administered statin among these cases. This study investigated the negative effects of simvastatin on skeletal muscle cells. We performed RNA sequencing analysis to determine gene expression in simvastatin-treated cells. Cell proliferation and migration were examined through cell cycle analysis and the transwell filter migration assay, respectively. Cytoskeleton rearrangement was examined through F-actin and tubulin staining. Western blot analysis was performed to determine the expression of cell cycle-regulated and cytoskeleton-related proteins. Transfection of small interfering RNAs (siRNAs) was performed to validate the role of cofilin and stathmin in the simvastatin-mediated inhibition of cell migration. The results revealed that simvastatin inhibited the proliferation and migration of skeletal muscle cells and affected the rearrangement of F-actin and tubulin. Simvastatin reduced the expression of cofilin and stathmin. The knockdown of both cofilin and stathmin by specific siRNA synergistically impaired cell migration. In conclusion, our results indicated that simvastatin inhibited skeletal muscle cell migration by reducing the expressions of cofilin and stathmin.

Graphene-based materials have gained remarkable attention in numerous disciplines owing to their unique electrochemical properties. Out of various hybridized nanocomposites, graphene-zirconia nanocomposite (GZ) was distinctive due to its biocompatibility. Zirconia nanoparticles serve as spacers that reduce the stacking of graphene and improve the electrochemical performance of the material. Considering that lungs and skin suffer the greatest exposure to nanoparticles, this study aimed to evaluate the cytotoxicity of the as-synthesized GZ nanocomposites on MRC5 (lung cells) and HaCaT (skin cells) via morphological observation and cell viability assay using 3-(4,5 dimethylthiazol-2-yl)-(2,5-diphenyltetrazolium bromide) tetrazolium (MTT). GZ-treated cells showed a comparable proliferation rate and morphology with untreated cells under microscopic evaluation. Based on MTT results, the IC 50 values of GZ were > 500 µg/ml for MRC5 and HaCaT cells. The excellent biocompatibility was the supremacy of GZ over other nanocomposites applied as electrode materials in biosensors. GZ was functionalized with biolinker for the detection of carcinoembryonic antigen (CEA). The proposed immunosensor exhibited good responses towards CEA detection, with a 4.25 pg/ml LOD and correlation coefficient of R 2  = 0.99 within a linear working range from 0.01 to 10 ng/ml. The performance of the immunosensor to detect CEA present in human serum was also evaluated. Good recovery of CEA was found, suggesting that the proposed immunosensor possess a high affinity to CEA even in a complex biological matrix, rendering it a promising sensing platform for real sample analysis and open a new way for the detection of cancer-associated proteins., (© 2021. The Author(s).)

Globally consumed kimchi is manufactured through fermenting cruciferous vegetables containing indole glucosinolates (IG). But few reports describe the IG metabolism during the fermentation. Here, we show that indole-3-carbinol (I3C), a breakdown product of IG, is transformed during the kimchi fermentation into 3,3'-diindolylmethane (DIM) and 2-(indol-3-ylmethyl)-3,3'-diindolylmethane (LTr1). LTr1 was found to kill the acute myeloid leukemia (AML) cells with FMS-like tyrosine kinase 3 (FLT3) receptor mutations, by inhibiting the FLT3 phosphorylation and the expression of downstream proteins (STAT5, ERK, and AKT). In the immune-depleted mice xenografted with human MV4-11 cells, LTr1 was demonstrated to reduce the tumor growth and synergize with sorafenib, an anti-AML agent in clinic. The work updates the chemical and biological knowledge about kimchi, and in particular establishes LTr1 as an FLT3 inhibitor that is effective and synergistic with sorafenib in treating AML., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Background: The increasing use of platelet-rich plasma (PRP) to treat muscle injuries raises concerns because transforming growth factor-beta (TGF-β) in PRP may promote fibrosis in the injured muscle and thus impair muscle regeneration., Purpose: To investigate whether suramin (a TGF-β inhibitor) can reduce muscle fibrosis to improve healing of the injured muscle after PRP treatment and identify the underlying molecular mechanism., Study Design: Controlled laboratory study., Methods: Myoblasts isolated from the gastrocnemius muscle of Sprague Dawley rats were treated with PRP or PRP plus suramin. MTT assays were performed to evaluate cell viability. The expression of fibrosis-associated proteins (such as type I collagen and fibronectin), Smad2, and phosphorylated Smad2 was determined using Western blot analysis and immunofluorescent staining. An anti-TGF-β antibody was employed to verify the role of TGF-β in fibronectin expression. Gastrocnemius muscles were injured through a partial transverse incision and then treated using PRP or PRP plus suramin. Hematoxylin and eosin staining was conducted to evaluate the healing process 7 days after the injury. Immunofluorescent staining was performed to evaluate fibronectin expression. Muscle contractile properties-fast-twitch and tetanic strength-were evaluated through electric stimulation., Results: PRP plus 25 μg/mL of suramin promoted myoblast proliferation. PRP induced fibronectin expression in myoblasts, but suramin reduced this upregulation. The anti-TGF-β antibody also reduced the upregulation of fibronectin expression in the presence of PRP. The upregulation of phosphorylated Smad2 by PRP was reduced by either the anti-TGF-β antibody or suramin. In the animal study, no significant difference was discovered in muscle healing between the PRP versus PRP plus suramin groups. However, the PRP plus suramin group had reduced fibronectin expression at the injury site. Fast-twitch strength and tetanic strength were significantly higher in the injured muscle treated using PRP or PRP plus suramin., Conclusion: Simultaneous PRP and suramin use reduced fibrosis in the injured muscle and promoted healing without negatively affecting the muscle's contractile properties. The underlying molecular mechanism may be associated with the phosphorylated Smad2 pathway., Clinical Relevance: Simultaneous PRP and suramin use may reduce muscle fibrosis without compromising muscle contractile properties and thus improve muscle healing.

There are health benefits from consuming cruciferous vegetables that release indole-3-carbinol (I3C), but the in vivo transformation of I3C-related indoles remains underinvestigated. Here we detail the post-ingestion conversion of I3C into antitumor agents, 2-(indol-3-ylmethyl)-3,3 ' -diindolylmethane (LTr1) and 3,3 ' -diindolylmethane (DIM), by conceptualizing and materializing the reaction flux derailing (RFD) approach as a means of unraveling these stepwise transformations to be non-enzymatic but pH-dependent and gut microbe-sensitive. In the upper (or acidic) gastrointestinal tract, LTr1 is generated through Michael addition of 3-methyleneindolium (3MI, derived in situ from I3C) to DIM produced from I3C via the formaldehyde-releasing (major) and CO 2 -liberating (minor) pathways. In the large intestine, 'endogenous' I3C and DIM can form, respectively, from couplings of formaldehyde with one and two molecules of indole (a tryptophan catabolite). Acid-producing gut bacteria such as Lactobacillus acidophilus facilitate the H + -promotable steps. This work updates our understanding of the merits of I3C consumption and identifies LTr1 as a drug candidate., (© The Author(s) 2021. Published by Oxford University Press on behalf of China Science Publishing & Media Ltd.)

An analytical formulation, referred to as conjugated Graetz problems, is developed to predict the temperature distribution and Nusselt numbers for the power-law fluid flowing in a double-pass concentric circular heat exchanger under sinusoidal wall fluxes. A new design of inserting an impermeable sheet into a concentric tube, in parallel, to conduct recycling double-pass operations has been studied theoretically in the fully developed region, resulting in substantial improvements in the performance of heat exchanger device. The analytical solution was derived using the complex functions by transforming the boundary value problem into ordinary differential equations with the aid of the Frobenius method. The influences of power-law index and impermeable-sheet position on average Nusselt numbers with various designs and operating parameters are also delineated. The theoretical predictions show that the heat transfer efficiency is considerably improved through operating the double-pass device compared to via a single-pass circular heat exchanger (where an impermeable sheet is not inserted). The economic feasibility of operating double-pass concentric circular heat exchanger for power-law fluids is exemplified by the ratio of the heat-transfer efficiency enhancement and the increment in power consumption. The double-pass effect from increasing the convective heat-transfer coefficient can compensate for the rise in power consumption, which serves as important economic advantage of this design.

Homeless individuals have many negative experiences with inequality regarding access to and the use of primary healthcare services, so policies to eliminate the disparities in and barriers to primary care access for these people are needed. The aim of this study was to explore the use and determinants of free hospital outpatient services for homeless people, in order to describe the provision of free healthcare policies for this vulnerable population in Taipei. One cross-sectional survey was conducted to recruit homeless people aged 45 years old and over in Taipei in 2018. A structured questionnaire was used, and face-to-face interviews were conducted by three social workers to collect the data. Finally, 129 participants were recruited in the study. The results show that 81.4% of the homeless people had made free hospital outpatient care visits (mean = 5.9 visits) in the last three months. An unadjusted logistic regression analysis showed that those homeless people who reported having usual healthcare providers, with higher depressive symptom scores, who used medication and had been hospitalized within one year, and had more chronic diseases, were significantly more likely to make free hospital outpatient visits. The adjusted logistic regression model indicates that homeless people with severe depressive symptoms (odds ratio (OR) = 9.32, 95% CI = 1.15-56.07), who had received medication (OR = 3.93; 95% CI = 1.06-14.52), and who had more than five chronic diseases (OR = 1.06, 95% CI = 1.35-13.27), were significantly more likely to make free hospital outpatient visits than their counterparts. The findings highlight that homeless people have higher healthcare requirements than the general population, and the healthcare system should pay more attention to factors associated with higher outpatient service use, such as homelessness, severe depressive symptoms, the receipt of medication and chronic diseases.

Background: Acute tendon injury can limit motion and thereby inhibit tendon healing. Positive results have been found after the use of platelet-rich plasma (PRP) to treat tendon injury; however, the early effects of PRP on tendon regeneration are not known., Purpose/hypothesis: The purpose of this study was to evaluate the effects of PRP releasate (PRPr) on the early stages of tendon healing in a rat partial tenotomy model. It was hypothesized that PRPr can promote early healing of an Achilles tendon in rats., Study Design: Controlled laboratory study., Methods: PRP was prepared by a 2-step method of manual platelet concentration from 10 rats. PRPr was isolated from the clotted preparation after activation by thrombin and was applied to an Achilles tendon on 1 side of 30 rats on the second day after partial tenotomy, with normal saline used as the control on the other side. Achilles tendon samples were harvested 5 and 10 days after tenotomy. At each time point, 15 Achilles tendon samples were obtained, of which 5 samples were evaluated by Masson trichrome staining, apoptosis, and cell proliferation, while the other 10 samples were tested for tensile strength using a material testing machine., Results: Compared with saline-treated control tendons, the PRPr-treated tendons showed increased collagen synthesis near the cut edge and fewer apoptotic cells ( P = .01). An immunohistochemical analysis revealed more Ki-67-positive cells but fewer cluster of differentiation (CD) 68 + (ED1 + ) macrophages in PRPr tendons compared with saline-treated tendons ( P < .01). Tendons treated with PRPr also showed higher ultimate tensile strength than those treated with saline ( P = .03)., Conclusion: PRPr treatment promotes tissue recovery in the early phase of tendon healing by stimulating tendon cell proliferation and collagen production while inhibiting cell apoptosis and CD68 + (ED1 + ) macrophage infiltration., Clinical Relevance: These findings suggest that with PRPr treatment, higher loads can be applied to the healing tendon at an earlier time, which can help the patient resume activity earlier., Competing Interests: One or more of the authors has declared the following potential conflict of interest or source of funding: This study received funding from the Chang Gung Memorial Hospital, Taoyuan City (CMRPG3C1361). AOSSM checks author disclosures against the Open Payments Database (OPD). AOSSM has not conducted an independent investigation on the OPD and disclaims any liability or responsibility relating thereto., (© The Author(s) 2021.)

Oxybenzone (OBZ), an ultraviolet light filter that is widely used in sunscreens and cosmetics, is an emerging contaminant found in humans and the environment. Recent studies have shown that OBZ has been detected in women's plasma, urine, and breast milk. However, the effects of OBZ exposure on oocyte meiosis have not been addressed. In this study, we investigated the detrimental effects of OBZ on oocyte maturation and the protective roles of melatonin (MT) in OBZ-exposed mouse models. Our in vitro and in vivo results showed that OBZ suppressed oocyte maturation, while MT attenuated the meiotic defects induced by OBZ. In addition, OBZ facilitated H3K4 demethylation by increasing the expression of the Kdm5 family of genes, elevating ROS levels, decreasing GSH, impairing mitochondrial quality, and disrupting spindle configuration in oocytes. However, MT treatment resulted in significant protection against OBZ-induced damage during oocyte maturation and improved oocyte quality. The mechanisms underlying the beneficial roles of MT involved reduction of oxidative stress, inhibition of apoptosis, restoration of abnormal spindle assembly and up-regulation of H3K4me3. Collectively, our results suggest that MT protects against defects induced by OBZ during mouse oocyte maturation in vitro and in vivo .

Objective: To investigate the effect of miR-29b-3p on apoptosis and proliferation of acute myeloid leukemia (AML) cells by targeting signal transducer and activator of transcription 3 (STAT3)., Methods: TargetScan and miRanda online databases were used to predict the binding sites of miR-29b-3p and STAT3 3'UTR. The targeting relationship between them was estimated by Dual-Luciferase reporter assay experiment. After miR-29b-3p over-expression, qPCR and Western blot were used to detect the expression of STAT3 mRNA and proteins, flow cytometry to determine the apoptosis of AML cells, and MTS to detect the changes of cell proliferation in each group., Results: Dual-Luciferase reporter assay confirmed that STAT3 was the target gene of miR-29b-3p. After miR-29b-3p overexpression, the expression of STAT3 mRNA and protein decreased. Compared with the control groups, the proliferation of AML cells in the overexpression group decreased and the apoptosis increased (P<0.05)., Conclusion: MiR-29b-3p can inhibit the proliferation and induce apoptosis of AML cells by down-regulating STAT3.

Osteoporosis is a global public health issue and its consequent effects are a growing concern worldwide. Caregivers generally experience occupational physical ailments and they have less of a tendency to engage in preventive health behaviors, leading them to be in a higher risk group for osteoporosis. This study aims to present a general profile of health literacy related to osteoporosis risks and identify its associated factors among disability institutional caregivers. A cross-sectional study with a structured questionnaire was used to collect information on 465 caregivers from seven disability care institutions regarding their awareness of the health literacy related to osteoporosis risks. The results indicate that the average literacy score related to osteoporosis risks among the respondents was 60 points (full score is 80 points), with 50-59 being the most common range (51.9%), followed by 60-69 points (43.5%), and 4.4% of cases had more than 70 points. A multivariate logistic regression model revealed that respondents' age (40-49 vs. 18-29; odds ratio (OR) = 2.53, 95% confidence interval (CI) = 1.31-4.87), education level (senior high vs. primary and junior high, OR = 2.00, 95% CI = 1.03-3.89; college and above vs. primary and junior high, OR = 3.66, 95% CI = 1.84-7.31), experience in undergoing a bone density test (OR = 1.94, 95% CI = 1.28-2.93), and poor physical fitness status (OR = 0.64, 95% CI = 0.43-0.95) were the significant predictors of the osteoporosis health literacy level. The osteoporosis health literacy of institutional caregivers is moderate, and there are many items that are worthy of attention in future health promotion programs. This study highlights risk factors related to a lower level of osteoporosis healthy literacy such as older age, less education, no experience of bone density test, and poor physical fitness that highlight the need to raise further awareness in order to improve caregivers' bone health.

This study investigates the screening for depressive symptoms among middle-aged and older homeless adults based on Patient Health Questionnaire-9 (PHQ-9) and examines the possible factors associated with their major depressive symptoms. A cross-sectional survey was employed, and research subjects included 129 homeless people aged 45 years old and over in Taipei Wanhua District and Taipei Main Station. We used a structured questionnaire and face-to-face interview conducted by three social workers to collect data in the analyses. The content of the questionnaire included an informed consent form, demographic characteristics, enabling and need factors of healthcare, and PHQ-9 of homeless people. Results revealed that 15.5% respondents were free of depressive symptoms, 16.3% had mild level (score 5-9), 31.8% had moderate level (score 10-14), 26.4% had moderately severe level (score 15-19), and 10.1% had severe level of depressive symptoms (score 20-27). Adopting a PHQ-9 score 10 as a cut-off point for major depressive symptoms, 68.3% of middle-aged and older homeless adults were the cases needing to be referred to healthcare settings for further recheck in the near future. A multiple regression analysis found gender, age, and usage of psychiatric outpatient care were associated with major depressive symptom occurrence. The female participants were less likely to have major depressive symptoms than the male participants (OR = 0.29, 95% CI = 0.09-0.96). The elderly participants were more likely to have major depressive symptoms than the aged 45-54 years (OR = 5.29, 95% CI = 1.44-19.41). Those participants who have ever used psychiatric outpatient care were significantly more correlated with the occurrence of major depressive symptoms than their counterparts (OR = 3.65, 95% CI = 1.46-9.09). The present study suggests that in the future health policy should eliminate the risk factors of depressive symptoms and improve mental healthcare access, to improve the health and wellbeing of the homeless population.

Knee osteoarthritis (KOA) is a prevalent disease, especially in the elderly. The present study examined the expression of matrix metalloproteinase-13 (MMP-13), NF-κBp65 and interleukin (IL)-lβ in the synovial tissues of KOA patients and the role of MMP-13 and the NF-κBp65 signalling pathway in KOA pathogenesis. A total of 100 KOA patients were enrolled in our hospital from December 2015 to December 2017 and were classified into either a mild KOA group (Outerbridge grade 1 and 2) or a severe KOA group (Outerbridge grade 3 and 4). Non-OA patients were included as controls. Synovial tissues from patients in both groups were collected for detection of the mRNA and protein expression of MMP-13, NF-κBp65 and IL-lβ. Synovial tissue slices were subjected to haematoxylin and eosin staining and immunohistochemistry (SP method). Cartilage tissues were observed under a light microscope after Safranin O-fast green staining. Reverse transcription-quantitative PCR and western blot analyses demonstrated that the expression of MMP-13, NF-κBp65 and IL-lβ in the mild and severe groups were substantially upregulated compared with the control group (all P<0.05). A positive correlation between MMP-13 and NF-κBp65 expression in the KOA synovial tissues was identified (P<0.05). Immunohistochemistry revealed that the expression of MMP-13 and NF-κBp65 was related to the severity of KOA (MMP-13: severe, 92.54%; moderate, 76.52%; control: 32.14%; and NF-κBp65: severe, 85.56%; moderate, 48.12%; control: 28.32%). This evidence indicated that the severity of KOA was related to MMP-13 and NF-κBp65 expression. The NF-κB signalling pathway may be activated during OA progression, which could upregulate the expression of MMP-13 and IL-1β and accelerate the deterioration of articular cartilage., (Copyright: © Zhao et al.)

This study employed the International Osteoporosis Foundation's One-Minute Osteoporosis Risk Test to examine factors related to the osteoporosis risk of institutional caregivers. In this cross-sectional study, a self-developed structured questionnaire comprising the One-Minute Osteoporosis Risk Test was used to obtain data on the caregivers' demographic data, health habits, working style, and osteoporosis risk. Seven disability welfare institutions were selected as research sites, and 465 copies of questionnaires were distributed to the institutions' employees, with 455 valid responses collected for a valid return rate of 98%. SPSS for Windows (Version 20.0) was used to analyze questionnaire data; descriptive-statistical frequency, a χ 2 test, and logistic regression were used to determine the correlation between demographic data, health habits, working style, and osteoporosis risk. The results revealed that primary risk factors include < 30 min of daily exercise (38%), lack of dairy product or calcium tablet intake (28%), and < 10 min of daily outdoor activity or not taking vitamin D supplements (29.9%). In total, 395 (86.8%) of the respondents scored less than 5 in the osteoporosis risk test; the remaining 60 (13.2%) scored 5 or higher, revealing a high risk of early osteoporosis. An independent variable analysis revealed that the risk factors of early osteoporosis include age, education level, having undergone bone density tests, prior disease diagnosis, long-term medication use, physical fitness, dietary habits, and average time of exposure to sunlight. In the multivariate analysis, poor physical fitness (odds ratio [OR] = 2.18, 95% confidence interval [CI]: 1.12-4.27, p = 0.023) and average daily time of exposure to sunlight (OR = 0.24, 95% CI: 0.59-2.59, p < 0.001) were significantly correlated with osteoporosis risk. In other words, respondents with poor physical fitness were 2.18 times as likely to have osteoporosis as those with good physical fitness, and those exposed to sunlight for 30 min or longer every day were 0.24 times as likely to have osteoporosis as those exposed to sunlight for less than 30 min every day. Accordingly, institutions must encourage employees to spend more time in the sun every day and improve their physical fitness through exercise., Competing Interests: The authors declare no conflict of interest.

Objective: To investigate the level of serum microRNA-609 and its clinical prognostic value in patients with thalassemia., Methods: One hundred and twenty-seven patients with thalassemia treated in our hospital from April 2017 to April 2018 were selected, 100 healthy persons were selected as control group. The changes of miR-609 were analyzed by RT-PCR, the relationship between miR-609 and clinical indicators of thalassemia was analyzed, and the prognostic risk factors of thalassemia were evaluated by multivariate logistic regression analysis., Results: The relative expression level of miR-609 in thalassemia patients was 3.17±0.24, which was significantly higher than that in control group (P<0.05). The levels of ALT, Plt and MCH in patients with high expression of miR-609 were significantly higher than those in patients with low expression of miR-609 (P<0.05). The levels of Hb and sICAM-1 in patients with high expression of miR-609 were significantly lower than those in patients with low expression of miR-609 (P<0.05). There was no correlation between the level of miR-609 and the patient's sex, age and AST (P>0.05). The incidence rate of mild anemia in high expression group was significantly lower than that in low expression group (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of moderate anemia (P>0.05). The number of patients with severe anemia in the miR-609 high expression group was higher than that in miR-609 low expression group (P<0.05). The incidence rate of dizziness, fatigue and fever in patients with miR-609 high expression group was significantly higher than those in patients with miR-609 low expression (P<0.05). There was no correlation between the level of miR-609 and the incidence rate of nausea in patients with thalassemia. ROC curve showed that the AUC value of microRNA-609 was 0.862, the sensitivity was 83.6%, and the specificity was 84.1%, which suggested that miR-609 had a high diagnostic value for thalassemia. Multivariate logistic regression analysis showed that MCH and mir-609 were risk factors for poor prognosis of thalassemia patients., Conclusion: The increased level of serum miR-609 in patients with thalassemia is a risk factor for poor prognosis and can be used as a reference index for evaluating the efficacy for patients.

Ethnopharmacological Relevance: Rosin, an exudate of conifer trees such as Pinus masscnlana (Pinaceae), has been used to treat psoriasis for nearly two thousand years in China despite its so far undefined pharmacology. Unfortunately, the rosin intoxication is noted from time to time, but the water-boiled rosin (WBR) has been documented to be safer. This study was performed to evaluate the in vivo anti-psoriasis efficacy of WBR., Materials and Methods: The main phytochemicals in WBR were quantified by high performance liquid chromatography (HPLC). WBR was evaluated in the imiquimod-induced psoriasis-like inflammation mouse model for its anti-psoriasis effect at 130, 260, and 390 mg/kg, which were set according to the dose used for patients. Through a combination of q-PCR, flow cytometry, and histopathological and immunohistochemical (IHC) analysis, the in vivo efficacy was assessed in terms of the psoriasis area severity index (PASI), epidermal keratinocyte proliferation, Th1 and Th17 cell numbers in spleen, and mRNA expressions of inflammatory cytokines., Result: Oral administration of WBR ameliorates the psoriasis-like dermatitis in the imiquimod-generated mouse model. In particular, WBR given at 260 or 390 mg/kg significantly restores the normal keratinization of dorsal lesion if compared with the untreated psoriatic mice. Such an effect was addressed to correlate to the Th1/Th17 cell reduction in spleen and the suppressed expression of IL-17A, IL-17F, IL-22, IL-23, TNF-α, K17, and proliferating cell nuclear antigen (PCNA) after the WBR administration., Conclusion: WBR is effective in the imiquimod-induced psoriasis-like inflammation mouse model with the efficacy arising from its proliferation inhibition of Th1/Th17 cells and epidermal keratinocytes via the down-regulation of the relevant inflammatory cytokines such as IL-23, IL-17A, and IL-17F. Collectively, WBR harvested and processed in the traditional manner is an efficacious psoriasis-treating agent., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat sports-related muscle injuries. However, NSAIDs were recently shown to impede the muscle healing process after acute injury. Migration of skeletal muscle cells is a crucial step during the muscle healing process. The present study was performed to investigate the effect and molecular mechanisms of action of ibuprofen, a commonly used NSAID, on the migration of skeletal muscle cells., Methods: Skeletal muscle cells isolated from the gastrocnemius muscle of Sprague-Dawley rats were treated with ibuprofen. MTT assay (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) was used to evaluate cell viability, and cell apoptosis was evaluated by TUNEL assay, after ibuprofen treatment. Skeletal muscle cell migration and spreading were evaluated using the transwell filter migration assay and F-actin staining, respectively. The protein expression of p130cas and CrkII, which are cell migration facilitating genes, was determined by western blot analysis. The overexpression of p130cas of muscle cells was achieved by p130cas vector transfection., Results: The results demonstrated that ibuprofen did not have a significant negative effect on cell viability and apoptosis. Ibuprofen inhibited the migration and spreading of skeletal muscle cells in a dose-dependent manner. Ibuprofen also dose-dependently decreased the protein expression of p130cas and CrkII. Furthermore, overexpression of p130cas resulted in the promotion of cell migration and spreading and counteracted ibuprofen-mediated inhibition., Conclusion: This study suggested that ibuprofen exerts a potentially adverse effect on the migration of skeletal muscle cells by downregulating protein expression of p130cas and CrkII. These results indicate a possible mechanism underlying the possible negative effect of NSAIDs on muscle regeneration.

As fracture healing is related to gene expression, fracture healing is prospected to be implicated in long non-coding RNAs (lncRNAs). This study focuses on the effects of epigenetic silencing of long non-coding RNA maternally expressed gene 3 (lncRNA MEG3) on fracture healing by regulating the Wnt/β-catenin signalling pathway. Genes expressed in fracture were screened using bioinformatics and the subcellular location of MEG3 was determined using FISH. Next, we successfully established tibia fracture (TF) models of C57BL/6J and Col2a1-ICAT mice and the effect of silencing lncRNA MEG3 on fracture healing was detected after TF mice were treated with phosphate buffer saline (PBS), MEG3 siRNA and scramble siRNA. X-ray imaging, Safranin-O/fast green and haematoxylin-eosin (HE) staining and histomorphometrical and biomechanical analysis were adopted to observe and to detect the fracture healing conditions. Additionally, the positive expression of collagen II and osteocalcin was examined using immunohistochemistry. At last, in the in vitro experiment, the relationship of MEG3 and the Wnt/β-catenin signalling pathway in fraction healing was investigated. MEG3 was located in the cell nucleus. In addition, it was found that MEG3 and the Wnt/β-catenin signalling pathway were associated with fraction healing. Moreover, silencing MEG3 was proved to elevate callus area and maximum bending load and to furthermore enhance the recanalization of bone marrow cavity. Finally, MEG3 knockdown elevated levels of Col10a1, Runx2, Osterix, Osteocalcin, Wnt10b and β-catenin/β-catenin whereas it reduced p-GSK-3β/GSK-3β levels. Taken together, our data supported that epigenetic silencing of lncRNA MEG3 could promote the tibia fracture healing by activating the Wnt/β-catenin signalling pathway., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

Objective: To investigate the influence of long non-coding ribonucleic acid (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on septic lung injury in mice and its mechanism, so as to provide references for the clinical prevention and treatment of septic lung injury in the future., Materials and Methods: A total of 60 male C57 mice were randomly divided into Control group (n=20), lipopolysaccharide (LPS) group (n=20), and LPS+MALAT1 siRNA group (n=20) using a random number table. The mouse model of septic lung injury was established via intraperitoneal injection of LPS (10 mg/kg), and the MALAT1 knockdown model was established via tail intravenous injection of MALAT1 siRNA. After 12 h, the lung was taken to measure the wet weight/dry weight ratio. Also, the activity of myeloperoxidase (MPO) in lung tissues was detected. The number of neutrophils and macrophages in bronchoalveolar lavage fluid (BALF) was detected via bronchoalveolar lavage. Moreover, the messenger RNA (mRNA) expression levels of inflammatory cytokines, including tumor necrosis factor-α (TNF-α), interleukin-1 (IL-1), and IL-6, in lung tissues were detected via Reverse Transcription-Polymerase Chain Reaction (RT-PCR). Finally, the expression level of p38 in lung tissues was detected via immunohistochemical staining, and the expressions of p38 mitogen-activated protein kinase (MAPK)/p65 nuclear factor-κB (NF-κB) signaling pathway-related proteins in lung tissues of mice were detected via Western blotting., Results: The expression of lncRNA MALAT1 in lung tissues of mice with septic lung injury was significantly increased (p<0.05). After knockdown of lncRNA MALAT1, the LPS-induced pathological injury of lungs could be improved, and the wet weight/dry weight ratio of lungs could be reduced (p<0.05). Compared with those in LPS group, the total number of inflammatory cells and the number of neutrophils and macrophages in BALF were significantly decreased in LPS+MALAT1 siRNA group (p<0.05), and the levels of inflammatory cytokines were also significantly inhibited (p<0.05). The immunohistochemical results manifested that the knockdown of lncRNA MALAT1 could inhibit the LPS-induced up-regulation of p38 in lung tissues in mice. According to the results of Western blotting, the p38 MAPK/p65 NF-κB signaling pathway was significantly activated in lung tissues in LPS group (p<0.05), while it was significantly suppressed after inhibition on lncRNA MALAT1 (p<0.05)., Conclusions: The knockdown of lncRNA MALAT1 can significantly improve the septic lung injury in mice, whose mechanism may be related to its inhibition on the p38 MAPK/p65 NF-κB signaling pathway.

The cell cycle inhibitor p27 Kip1 is a tumor suppressor via the inhibition of CDK complexes in the nucleus. However, p27 also plays other functions in the cell and may acquire oncogenic roles when located in the cytoplasm. Activation of oncogenic pathways such as Ras or PI3K/AKT causes the relocalization of p27 in the cytoplasm, where it can promote tumorigenesis by unclear mechanisms. Here, we investigated how cytoplasmic p27 participates in the development of non-small cell lung carcinomas. We provide molecular and genetic evidence that the oncogenic role of p27 is mediated, at least in part, by binding to and inhibiting the GTPase RhoB, which normally acts as a tumor suppressor in the lung. Genetically modified mice revealed that RhoB expression is preferentially lost in tumors in which p27 is absent and maintained in tumors expressing wild-type p27 or p27 CK- , a mutant that cannot inhibit CDKs. Moreover, although the absence of RhoB promoted tumorigenesis in p27 -/- animals, it had no effect in p27 CK- knock-in mice, suggesting that cytoplasmic p27 may act as an oncogene, at least in part, by inhibiting the activity of RhoB. Finally, in a cohort of lung cancer patients, we identified a subset of tumors harboring cytoplasmic p27 in which RhoB expression is maintained and these characteristics were strongly associated with decreased patient survival. Thus, monitoring p27 localization and RhoB levels in non-small cell lung carcinoma patients appears to be a powerful prognostic marker for these tumors. Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (Copyright © 2018 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Polyketide-polyketide hybrids are unique natural products with promising bioactivity, but the hybridization processes remain poorly understood. Herein, we present that the biosynthetic pathways of two immunosuppressants, dalmanol A and acetodalmanol A, result from an unspecific monooxygenase triggered hybridization of two distinct polyketide (naphthalene and chromane) biosynthetic gene clusters. The orchestration of the functional dimorphism of the polyketide synthase (ChrA) ketoreductase (KR) domain (shortened as ChrA KR) with that of the KR partner (ChrB) in the bioassembly line increases the polyketide diversity and allows the fungal generation of plant chromanes ( e.g. , noreugenin) and phloroglucinols ( e.g. , 2,4,6-trihydroxyacetophenone). The simultaneous fungal biosynthesis of 1,3,6,8- and 2-acetyl-1,3,6,8-tetrahydroxynaphthalenes was addressed as well. Collectively, the work may symbolize a movement in understanding the multiple-gene-cluster involved natural product biosynthesis, and highlights the possible fungal generations of some chromane- and phloroglucinol-based phytochemicals.

Background: Platelet-rich plasma (PRP) contains various cytokines and growth factors that may be beneficial to the healing process of injured muscle. Based on the authors' previous study, PRP releasate can promote proliferation and migration of skeletal muscle cells in vitro, so animal studies are performed to support the use of PRP to treat muscle injury in vivo., Purpose: To investigate the effect of PRP releasate on regeneration of injured muscle, as well as its effect on inflammatory reaction and cell apoptosis, in the early stages of the muscle-healing process., Study Design: Controlled laboratory study., Methods: The gastrocnemius muscles of Sprague-Dawley rats were injured by partial transverse incision and then treated with PRP releasate. Hematoxylin and eosin stain was used to evaluate the healing process of injured muscle at 2, 5, and 10 days after injury. TUNEL assay was used to evaluate the cell apoptosis of injured muscle after PRP releasate treatment. Immunohistochemistry was used to stain the CD68-positive cells during the healing process. Muscle contractile properties, including fast-twitch and tetanic strength, were evaluated by electric stimulation., Results: The results revealed that PRP releasate treatment could enhance the muscle-healing process and decrease CD68-positive cells and apoptotic cells. Furthermore, the tetanic strength was significantly higher in injured muscle treated with PRP releasate., Conclusion: In conclusion, PRP releasate could enhance the healing process of injured muscle and decrease inflammatory cell infiltration as well as cell apoptosis., Clinical Relevance: PRP promotes skeletal muscle healing in association with decreasing inflammation and apoptosis of injured skeletal muscle. These findings provide in vivo evidence to support the use of PRP to treat muscle injury.

Highly efficient decontamination of heavily toxic Cr 2 O 7 2- from water remains a serious task for public health and ecosystem protection. An easily regenerative and reused sorbent with suitable porosity may address this task. Herein, a series of water-stable and ecofriendly metal-organic frameworks (MOFs) with large surface areas were assessed for their ability to adsorb and separate Cr 2 O 7 2- from aqueous solutions. Among these tested MOFs, NU-1000 shows an extraordinary capability to efficiently capture (within 3 min) Cr 2 O 7 2- with a sorption capacity of up to 76.8 mg/g, which is the largest one for the neutral MOF-based Cr 2 O 7 2- sorbents. NU-1000 also shows remarkable selectivity for Cr 2 O 7 2- capture and can effectively reduce the Cr(VI) concentration from 24 ppm to 60 ppb, which is below the acceptable limit for the drinking water standard (100 ppb by the U.S. Environmental Protection Agency). Moreover, this adsorbent can be easily regenerated by Soxhlet extraction with an acidic methanol solution (2.5 M HCl) and can be reused at least three times without a significant loss of it adsorption ability. More intriguingly, NU-1000 can also serve as an efficient photoluminescent probe for the selective detection of Cr 2 O 7 2- in aqueous media. The Cr 2 O 7 2- detection limit is as low as 1.8 μM, and the linear range is from 1.8 to 340 μM. Our work shows that NU-1000 is a unique material combining both efficient sorption and exceptional fluorescent sensing of Cr 2 O 7 2- in aqueous media.