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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.