Acetylated KHSRP impairs DNA-damage-response-related mRNA decay and facilitates prostate cancer tumorigenesis.

Androgen-regulated DNA damage response (DDR) is one of the essential mechanisms in prostate cancer (PCa), a hormone-sensitive disease. The heterogeneous nuclear ribonucleoprotein K (hnRNPK)-homology splicing regulatory protein known as far upstream element-binding protein 2 (KHSRP) is an RNA-binding protein that can attach to AU-rich elements in the 3' untranslated region (3'-UTR) of messenger RNAs (mRNAs) to mediate mRNA decay and emerges as a critical regulator in the DDR to preserve genome integrity. Nevertheless, how KHSRP responds to androgen-regulated DDR in PCa development remains unclear. This study found that androgen can significantly induce acetylation of KHSRP, which intrinsically drives tumor growth in xenografted mice. Moreover, enhanced KHSRP acetylation upon androgen stimuli impedes KHSRP-regulated DDR gene expression, as seen by analyzing RNA sequencing (RNA-seq) and Gene Set Enrichment Analysis (GSEA) datasets. Additionally, NAD-dependent protein deacetylase sirtuin-7 (SIRT7) is a promising deacetylase of KHSRP, and androgen stimuli impairs its interaction with KHSRP to sustain the increased KHSRP acetylation level in PCa. We first report the acetylation of KHSRP induced by androgen, which interrupts the KHSRP-regulated mRNA decay of the DDR-related genes to promote the tumorigenesis of PCa. This study provides insight into KHSRP biology and potential therapeutic strategies for PCa treatment, particularly that of castration-resistant PCa.

Correlational analysis of PLIN1 with inflammation in diabetic foot ulcer wounds.

BACKGROUND: The persistent presence of inflammation is a recognized pathogenic mechanisms of diabetic foot ulcers (DFUs). We aimed to investigate the expression of PLIN1 in tissues from DFU patients and assess its potential association with inflammation-induced damage. METHODS: We performed transcriptome sequencing and correlation analysis of the foot skin from patients with or without DFUs. Additionally, we examined the correlation between PLIN1 and related inflammatory indicators by analyzing PLIN1 expression in tissue and serum samples and through high-glucose stimulation of keratinocytes (HaCaT cells). RESULTS: PLIN1 is upregulated in the tissue and serum from DFU patients. Additionally, PLIN1 shows a positive correlation with leukocytes, neutrophils, monocytes, C-reactive protein, and procalcitonin in the serum, as well as IL-1ß and TNF-α in the tissues. Experiments with Cells demonstrated that reduced expression of PLIN1 leads to significantly decreased expression of iNOS, IL-1ß, IL-6, IL-18, and TNF-α. PLIN1 may mediate wound inflammatory damage through the NF-κB signaling pathway. CONCLUSION: Our findings suggest that PLIN1 mediates the inflammatory damage in DFU, offering new prospects for the treatment of DFU.

Super-enhancer-driven LIF promotes the mesenchymal transition in glioblastoma by activating ITGB2 signaling feedback in microglia.

BACKGROUND: The mesenchymal (MES) subtype of glioblastoma (GBM) is believed to be influenced by both cancer cell-intrinsic alterations and extrinsic cellular interactions, yet the underlying mechanisms remain unexplored. METHODS: Identification of microglial heterogeneity by bioinformatics analysis. Transwell migration, invasion assays, and tumor models were used to determine gene function and the role of small molecule inhibitors. RNA sequencing, chromatin immunoprecipitation, and dual-luciferase reporter assays were performed to explore the underlying regulatory mechanisms. RESULTS: We identified the inflammatory microglial subtype of tumor-associated microglia (TAM) and found that its specific gene ITGB2 was highly expressed in TAM of MES GBM tissues. Mechanistically, the activation of ITGB2 in microglia promoted the interaction between the SH2 domain of STAT3 and the cytoplasmic domain of ITGB2, thereby stimulating the JAK1/STAT3/IL-6 signaling feedback to promote the MES transition of GBM cells. Additionally, microglia communicated with GBM cells through the interaction between the receptor ITGB2 on microglia and the ligand ICAM-1 on GBM cells, while an increased secretion of ICAM-1 was induced by the proinflammatory cytokine LIF. Further studies demonstrated that inhibition of CDK7 substantially reduced the recruitment of SNW1 to the super-enhancer of LIF, resulting in transcriptional inhibition of LIF. We identified notoginsenoside R1 as a novel LIF inhibitor that exhibited synergistic effects in combination with temozolomide. CONCLUSIONS: Our research reveals that the epigenetic-mediated interaction of GBM cells with TAM drives the MES transition of GBM and provides a novel therapeutic avenue for patients with MES GBM.

Vitamin D inhibits tamoxifen-induced non-alcoholic fatty liver disease through a nonclassical estrogen receptor/liver X receptor pathway.

Non-alcoholic Fatty Liver Disease (NAFLD) is one of the common side effects of tamoxifen treatment for estrogen receptor-positive breast cancer, and is representative of disorders of energy metabolism. Fatty liver is induced after tamoxifen (TAM) inhibition of estrogen receptor activity, but the exact mechanism is not clear. This study investigated the effects and mechanisms of TAM-induced steatosis in the liver. The effects and mechanisms of TAM on hepatocyte lipid metabolism were assessed using C57BL/6 female mice and human hepatoma cells. TAM promoted fat accumulation in the liver by upregulation of Srebp-1c expression. Regarding the molecular mechanism, TAM promoted the recruitment of the auxiliary transcriptional activator, p300, and dissociated the auxiliary transcriptional repressor, nuclear receptor corepressor (NCOR), of the complexes, which led to enhancement of Srebp-1c transcription and an increase of triglyceride (TG) synthesis. Vitamin D (VD), a common fat-soluble vitamin, can decrease TAM-induced NAFLD by promoting p300 dissociation and NCOR recruitment. Tamoxifen promoted the recruitment and dissociation of co-transcription factors on the LXR/ER/RXR receptor complex, leading to a disorder of liver lipid metabolism. VD interfered with TAM-induced liver lipid metabolism disorders by reversing this process.

Intratumoral and Peritumoral Multiparametric MRI-Based Radiomics Signature for Preoperative Prediction of Ki-67 Proliferation Status in Glioblastoma: A Two-Center Study.

RATIONALE AND OBJECTIVES: To assess the predictive ability of intratumoral and peritumoral multiparametric magnetic resonance imaging (MRI)-based radiomics signature (RS) for preoperative prediction of Ki-67 proliferation status in glioblastoma. MATERIALS AND METHODS: A total of 205 patients with glioblastoma at two institutions were retrospectively analyzed. Data from institution 1 (n = 158) were used to develop the predictive model, and as an internal test dataset, data from institution 2 (n = 47) constitute the external test dataset. Feature selection was performed using spearman correlation coefficient, univariate ranking method, and the least absolute shrinkage and selection operator algorithm. RSs were established using a logistic regression algorithm. The predictive performance of the RSs was assessed using calibration curve, decision curve analysis (DCA), and area under the curve (AUC). RESULTS: In the RSs based on single-parametric (contrast-enhanced T1-weighted image, T2-weighted image, or apparent diffusion coefficient maps), the AUCs of intratumoral, peritumoral, and combined area (intratumoral and peritumoral) were 0.60-0.67, with no significant difference among them. The RSs that using multiparametric features (integrating the previously mentioned three sequences) showed improved AUC compared to the single-parametric RSs; AUC reached 0.75-0.89. Among them, the multiparametric RS based on radiomics features of the combined area (Multi-Com) exhibited the highest performance, with an internal test dataset AUC of 0.89 (95% confidence interval (CI) 0.75-1.00) and an external test dataset AUC of 0.88 (95% CI 0.78-0.97). The calibration curve and DCA display RS (Multi-Com) have good calibration ability and clinical applicability. CONCLUSION: The multiparametric MRI-based RS combining intratumoral and peritumoral features can serve as a noninvasive and effective tool for preoperative assessment of Ki-67 proliferation status in glioblastoma.

Super-enhancers complexes zoom in transcription in cancer.

Super-enhancers (SEs) consist of multiple typical enhancers enriched at high density with transcription factors, histone-modifying enzymes and cofactors. Oncogenic SEs promote tumorigenesis and malignancy by altering protein-coding gene expression and noncoding regulatory element function. Therefore, they play central roles in the treatment of cancer. Here, we review the structural characteristics, organization, identification, and functions of SEs and the underlying molecular mechanism by which SEs drive oncogenic transcription in tumor cells. We then summarize abnormal SE complexes, SE-driven coding genes, and noncoding RNAs involved in tumor development. In summary, we believe that SEs show great potential as biomarkers and therapeutic targets.

Metallochaperone protein OsHIPP17 regulates the absorption and translocation of cadmium in rice (Oryza sativa L.).

Heavy metal-associated isoprenylated plant proteins (HIPPs) play vital roles in regulating heavy metal responding activities in plants. Yet only a handful of studies have characterized the functions of HIPPs. In this study, a novel HIPP member OsHIPP17 was functionally characterized, which was involved in the tolerance of yeast and plants to cadmium (Cd). The Cd accumulation in yeast cells was increased due to the overexpression of OsHIPP17. Nevertheless, the overexpression of OsHIPP17 in Arabidopsis thaliana resulted in compromised growth under Cd stress. Meanwhile, the mutation of OsHIPP17 resulted in 38.9-40.9 % increase of Cd concentration in rice roots as well as 14.3-20.0 % decrease of Cd translocation factor. Further investigation of the genes responsible for Cd absorption and transporter indicated that the expression levels of these genes were also perturbed. In addition, two OsHIPP17-interacting proteins, OsHIPP24 and OsLOL3 were identified in a yeast two hybrid assay. Further analysis of their functions revealed that OsHIPP24 or OsLOL3 may be involved in the regulation of Cd tolerance by OsHIPP17 in rice. All above results implied that OsHIPP17 may affect Cd resistance by regulating the absorption and translocation of Cd in rice.

Cubane-type tungsten-iron-sulfur clusters with a nitrogen atom in the core: terminal ligand substitutions and redox behaviors.

The lack of M-Fe-S (M = Mo or W) clusters incorporating a second period (2p) atom in the core has resulted in limited investigations and poor understanding of the physical and chemical properties of the M-Fe-S clusters closely related to the FeMo cofactor. In this work, systematic studies have been carried out to explore the chemical reactivities at the terminal ligand sites and the redox properties of a series of clusters comprising a [WFe3S3N] cubane core, based on the previously developed cluster [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]1-. Substitutions of the terminal chlorides with ethanethiolate, methanethiolate, thiophenolate, p-thiocresolate and azide occurred smoothly, while the replacement of the chlorides with carbene ligands required the reduction of the precursor into [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]2- first. The reduced cluster core could also be supported by thiophenolates as terminal ligands, but not thiolates or azides. It is remarkable that the thiophenolate ligated reduced cluster can be synthesized from the precursor [(Tp*)WFe3S3(µ3-NSiMe3)Cl3]1-via different synthetic routes, either reduction followed by substitution or substitution followed by reduction, either in situ or stepwise. This work indicates that terminal ligands contribute significantly to determine the chemical and physical properties of the clusters, even though they might affect the cluster core to a limited extent from a structural point of view, which raises the possibility of delicate control in regulating the physical/chemical properties of M-Fe-S clusters with a heteroleptic core incorporating 2p atom(s).

Protective Effect of Chinese Bayberry (Myrica rubra Sieb. et Zucc.) Pomace Wine on Oxidative Stress of Hydrogen Peroxide by Regulating Keap1/Nrf2 Pathway in HepG2 Cells.

Chinese bayberry (Myrica rubra Sieb. et Zucc.) pomace wine (CPW) is fruity and rich in bioactive compounds, with high nutritional value and antioxidant activities. This study aims to investigate the protective effect of CPW on the oxidative damage induced by hydrogen peroxide in human hepatocellular carcinoma (HepG2) cells and CPW's possible underlying mechanism. The fluorescence assay results revealed that CPW pre-treatment inhibited intracellular reactive oxygen species (ROS) accumulation in H2O2-induced HepG2 cells and cell membrane injury. Meanwhile, CPW remarkably enhanced the activity of antioxidant enzymes including superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR), and the content of glutathione (GSH). Moreover, CPW pretreatment significantly regulated the expression of Kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid 2-related factor 2 (Nrf2) pathway-associated genes (Keap1, Nrf2, NADPH quinone oxidoreductase I (NQO1), and heme oxygenase-1 (HO-1)) and its downstream antioxidant genes (SOD, CAT, GSH, and the glutamate-cysteine ligase catalytic (GCLC) subunit) in HepG2 cells. These data demonstrated that CPW prevented H2O2-induced oxidative stress by regulating the Keap1/Nrf2 signaling pathway.

Bioinformatic and functional analysis of OsDHN2 under cadmium stress.

As a toxic heavy metal, cadmium (Cd) is one of the principal pollutants influencing rice productivity and food security. Despite several studies, the underlying mechanism of Cd response in plants remains largely unclear. Dehydrins are part of the late embryogenesis abundant (LEA) family which protect plants against abiotic stresses. In this study, a Cd-responsive LEA gene, OsDHN2, was functionally characterized. The chromosome localization results indicated that OsDHN2 was located on chromosome 2 of rice. Meanwhile, cis-acting elements, such as MBS (MYB binding site involved in drought-inducibility), ARE (anaerobic induction), and ABRE (abscisic acid), were present in the OsDHN2 promoter region. Expression pattern analysis also showed that OsDHN2 expression was induced in both roots and shoots under Cd stress. Overexpression of OsDHN2 improved Cd tolerance and reduced Cd concentration in yeast. Moreover, increased expression levels of SOD1, CTA1, GSH1, or CTT1 were found in transgenic yeast under Cd stress, suggesting the increased antioxidant enzymatic activities. These results suggested that OsDHN2 is a Cd-responsive gene that has the potential to improve resistance to Cd in rice.

Delivery of curcumin in a carboxymethyl cellulose and hydroxypropyl methyl cellulose carrier: Physicochemical properties and biological activity.

Curcumin solid dispersions (Cur SDs) were prepared using hydroxypropyl methyl cellulose (HPMC) and sodium carboxymethyl cellulose (CMC) at different dosages. The results of Fourier transform infrared spectroscopy and Raman spectroscopy showed that the characteristic peak of curcumin shifted, and the addition of CMC enhanced this phenomenon. The addition of CMC reduced the contact angle, increased the surface free energy, and improved the solubility of Cur SDs. These changes were positively correlated with the amount of CMC. The surface morphology of Cur SDs changed from needle-like to sheet-like as observed by scanning electron microscopy. Cur SDs prepared by CMC and HPMC retained good biological activity. HT-29 human colon cancer cell analysis showed that the addition of CMC significantly improved the anti-proliferation effect of Cur SDs, thus enhancing the bioavailability of curcumin. Solid dispersions made with CMC and HPMC will be a promising hydrocolloid carrier to improve oral bioavailability and efficacy of curcumin.

The Controlled Release and Prevention of Abdominal Adhesion of Tannic Acid and Mitomycin C-Loaded Thermosensitive Gel.

Postoperative abdominal adhesion is one of the most common complications after abdominal surgery. A single drug or physical barrier treatment does not achieve the ideal anti-adhesion effect. We developed a thermosensitive hydrogel (PPH hydrogel) consisting of poloxamer 407 (P407), poloxamer (P188), and hydroxypropyl methylcellulose (HPMC) co-blended. An injectable thermosensitive TA/MMC-PPH hydrogel was obtained by loading tannic acid (TA) with an anti-inflammatory effect and mitomycin C (MMC), which inhibits fibroblast migration or proliferation. The optimal prescriptions of PPH hydrogels with a suitable gelling time (63 s) at 37 °C was 20% (w/v) P407, 18% (w/v) P188, and 0.5% (w/v) HPMC. The scanning electron microscopy (SEM) revealed that the PPH hydrogel had a three-dimensional mesh structure, which was favorable for drug encapsulation. The PPH hydrogel had a suitable gelation temperature of 33 °C, a high gel strength, and complicated viscosity at 37 °C, according to the rheological analysis. In vitro release studies have shown that the PPH hydrogel could delay the release of TA and MMC and conform to the first-order release rate. Anti-adhesion tests performed on rats in vivo revealed that TA/MMC-PPH hydrogel significantly reduced the risk of postoperative adhesion. In conclusion, the TA/MMC-PPH hydrogel prepared in this study showed an excellent performance in both controlled drug release and anti-adhesive effects. It can be used as a protocol to prevent or reduce postoperative abdominal adhesion.

PTK6 inhibits autophagy to promote uveal melanoma tumorigenesis by binding to SOCS3 and regulating mTOR phosphorylation.

Autophagy dysfunction is one of the common causes of tumor formation and plays an important role in uveal melanoma (UM). However, little is known about the regulatory mechanisms of autophagy in UM. Here, we show that PTK6 can promote the proliferation, migration, and invasion of UM cells by inhibiting autophagy. SOCS3 can inhibit the proliferation, migration, and invasion of UM cells. Overexpression of SOCS3 can partially rescue the PTK6-induced promotion of UM cell proliferation, migration, and invasion. Mechanistically, PTK6 can bind to SOCS3, and SOCS3 can downregulate the expression of PTK6. Furthermore, PTK6 can upregulate the phosphorylation of mTOR to inhibit autophagy. Taken together, our findings demonstrate the functions of PTK6 and SOCS3 in UM cells and targeting the SOCS3-PTK6 signaling axis might be a novel and promising therapeutic strategy for patients with UM.

WZ35 inhibits gastric cancer cell metastasis by depleting glutathione to promote cellular metabolic remodeling.

This study aimed at elucidating the crosstalk between redox reaction and metabolic remodeling through uncovering the mechanism underlying WZ35-mediated reactive oxygen species (ROS) production and regulation of amino acid metabolism to inhibit gastric cancer (GC) cell metastasis. The activity and biosafety of curcumin analog, WZ35, were verified in vitro and in vivo. The potential molecular mechanism underlying WZ35-mediated enhanced radiotherapeutic sensitivity by reduced Glutathione (GSH) depletion was elucidated by RNA sequencing, single-cell sequencing (scRNA-seq), metabolic mass spectrometry, and other molecular experiments. Compared to curcumin, WZ35 proved more potent anti-proliferative and anti-metastasis properties. Importantly, we demonstrated that WZ35 could consume GSH in multiple ways, including by reduction of raw materials and consumption reserves, inhibition of reformation, and enhanced decomposition. Mechanistically, we identify that WZ35 maintains the GSH depletion phenotype through the ROS-YAP-AXL-ALKBH5-GLS2 loop, further backing the relevance of metabolic remodeling in the tumor microenvironment with tumor metastasis and the role of m6A in tumor metastasis. Collectively, our study identified WZ35 as a novel GSH depletion agent and a previously undiscovered GSH depletion loop mechanism in GC cell metastasis.

Sequential anti-inflammatory and osteogenic effects of a dual drug delivery scaffold loaded with parthenolide and naringin in periodontitis.

PURPOSE: Our pilot study showed that a 3-dimensional dual drug delivery scaffold (DDDS) loaded with Chinese herbs significantly increased the regenerated bone volume fraction. This study aimed to confirm the synergistic anti-inflammatory and osteogenic preclinical effects of this system. METHODS: The targets and pathways of parthenolide and naringin were predicted. Three cell models were used to assess the anti-inflammatory effects of parthenolide and the osteogenic effects of naringin. First, the distance between the cementoenamel junction and alveolar bone crest (CEJ-ABC) and the bone mineral density (BMD) of surgical defects were measured in a rat model of periodontitis with periodontal fenestration defects. Additionally, the mRNA expression levels of matrix metallopeptidase 9 (MMP9) and alkaline phosphatase (ALP) were measured. Furthermore, the number of inflammatory cells and osteoclasts, as well as the protein expression levels of tumor necrosis factor-alpha (TNF-α) and levels of ALP were determined. RESULTS: Target prediction suggested prostaglandin peroxidase synthase (PTGS2) as a potential target of parthenolide, while cytochrome P450 family 19 subfamily A1 (CYP19A1) and taste 2 receptor member 31 (TAS2R31) were potential targets of naringin. Parthenolide mainly targeted inflammation-related pathways, while naringin participated in steroid hormone synthesis and taste transduction. In vitro experiments revealed significant anti-inflammatory effects of parthenolide on RAW264.7 cells, and significant osteogenic effects of naringin on bone marrow mesenchymal stem cells and MC3T3-E1 cells. DDDS loaded with parthenolide and naringin decreased the CEJ-ABC distance and increased BMD and ALP levels in a time-dependent manner. Inflammation was significantly alleviated after 14 days of DDDS treatment. Additionally, after 56 days, the DDDS group exhibited the highest BMD and ALP levels. CONCLUSIONS: DDDS loaded with parthenolide and naringin in a rat model achieved significant synergistic anti-inflammatory and osteogenic effects, providing powerful preclinical evidence.

Changes in clinical and CT manifestations related to liver abscesses in patients with vs. without basic diabetes mellitus before and after CT-guided interventional therapy: An observational study

Abstract Purpose: To explore differences in the changes of clinical and CT manifestations related to liver abscess before and after CT-guided interventional therapy between patients with and without Diabetes Mellitus (DM). Materials and methods: Fifty-eight consecutive patients with liver abscesses were retrospectively enrolled in this study. All patients underwent upper abdominal contrast-enhanced CT scans before and after CT-guided interventional therapy. They were divided into two groups including the DM group (n = 30) and the Non-DM group (n = 28) if the liver abscess occurred in patients with and without DM, respectively. The changes in the clinical and CT manifestations related to liver abscess after CT-guided interventional therapy in both groups were statistically analyzed. Results: After CT-guided interventional therapy, the length of hospital stay, white blood cell recovery time and drainage tube removal time in the DM group were longer than in the Non-DM group (all p-values < 0.05). The incidence of postoperative complications in the DM group was higher than in the Non-DM group (p < 0.05). As shown on CT, the postoperative reduced percentage of maximum diameter of abscess cavity and the reduction rate of edema band surrounding the liver abscess in the DM group were smaller than in the Non-DM group (both p-values < 0.05). The time intervals of the previous characteristic changes on CT before and after interventional therapy in the DM group were longer than in the Non-DM group (all p-values < 0.05). Conclusions: The liver abscesses patients with DM could not have a faster recovery and better therapeutic effect than those without DM after the CT-guided interventional therapy.

Kinematic analysis of music's influence on body expression / Análise cinemática da influência musical sobre a expressão corporal / Análisis cinemático de la influencia musical en la expresión corporal

ABSTRACT Introduction Dance is a combination of strength and beauty. Improving the expression of body movements in dance can improve the artistic quality of the performers and provide a greater visual experience to its spectators. Objective Explore the influence of music on dancers' upper limb movement expression through kinematic analysis based on movement mechanics. Methods The factors influencing the expression of body movements and sports training in the dance process were investigated via a questionnaire. A group of 20 volunteers performed a movement performance only through a specific rhythm, while the experimental group combined the full music with the dance moves. After a set of four dance movements, the completion time, trajectory length, speed, and acceleration of the upper limbs were recorded and rated, analyzing the fluency of the two movement groups. Results Dance movement does not interfere as much with the rhythmic control of professional dancers; however, it impacts their fluency, range, and motion. Conclusion With the cooperation of music, the dancers' movements were more harmonious and smoother, bringing a better expressive effect to the upper limbs. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução A dança é uma combinação de força e beleza. Aprimorar a expressão dos movimentos corporais na dança pode melhorar a qualidade artística dos intérpretes e proporcionar uma maior experiência visual aos seus espectadores. Objetivo Explorar a influência da música na expressão dos movimentos dos membros superiores de dançarinos, por análise cinemática baseada na mecânica do movimento. Métodos Os fatores de influência da expressão dos movimentos corporais e do treinamento esportivo no processo de dança foram investigados via questionário. Um grupo de 20 voluntários efetuou uma performance de movimento apenas através de um ritmo específico, enquanto o grupo experimental combinou com a música completa ao movimento de dança. Após um conjunto de quatro movimentos de dança, o tempo de conclusão, o comprimento da trajetória, a velocidade e a aceleração dos membros superiores foram gravadas e classificados, analisando a fluência dos dois grupos de movimento. Resultados O movimento da dança não interfere tanto no controle rítmico dos dançarinos profissionais, porém tem impacto na fluência e na amplitude e movimento dos bailarinos. Conclusão Com a cooperação da música, os movimentos dos dançarinos mostraram-se mais harmônicos e suaves, trazendo um melhor efeito expressivo aos membros superiores. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción La danza es una combinación de fuerza y belleza. Mejorar la expresión de los movimientos corporales en la danza puede optimizar la calidad artística de los intérpretes y proporcionar una mayor experiencia visual a sus espectadores. Objetivo Explorar la influencia de la música en la expresión de los movimientos de las extremidades superiores de los bailarines mediante un análisis cinemático basado en la mecánica del movimiento. Métodos Se investigaron mediante un cuestionario los factores que influyen en la expresión de los movimientos corporales y el entrenamiento deportivo en el proceso de la danza. Un grupo de 20 voluntarios realizó una actuación de movimiento sólo mediante un ritmo específico, mientras que el grupo experimental combinó con la música completa el movimiento de baile. Tras un conjunto de cuatro movimientos de danza, se registraron y clasificaron el tiempo de finalización, la longitud de la trayectoria, la velocidad y la aceleración de los miembros superiores, analizando la fluidez de los dos grupos de movimientos. Resultados El movimiento de la danza no interfiere tanto en el control rítmico de los bailarines profesionales, pero sí repercute en la fluidez y la amplitud de movimiento de los bailarines. Conclusión Con la colaboración de la música, los movimientos de los bailarines se mostraron más armoniosos y suaves, aportando un mejor efecto expresivo a los miembros superiores. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Comparison of Mitochondrial Adenosine Triphosphate-Sensitive Potassium Channel High- vs Low-Affinity Sulfonylureas and Cardiovascular Outcomes in Patients With Type 2 Diabetes Treated With Metformin.

Importance: Sulfonylureas are frequently used as add-on to metformin in type 2 diabetes (T2D), and individual sulfonylurea agents carry different risks of cardiovascular disease. Sulfonylureas' different affinities to cardiac mitochondrial adenosine triphosphate-sensitive potassium (mitoKATP) channels have been speculated to account for the intraclass difference in cardiovascular risk from in vitro and ex vivo studies; however, this hypothesis has not been assessed in a general population with diabetes receiving sulfonylureas added to metformin. Objective: To compare the risk of myocardial infarction (MI), ischemic stroke, or cardiovascular death in patients with T2D treated with mitoKATP channel high-affinity sulfonylureas and low-affinity sulfonylureas as add-on to metformin. Design, Setting, and Participants: This is a new-user, active-comparator, and propensity score-matched cohort study with analysis of the Taiwanese Diabetes Mellitus Health Database from 2006, to 2017. Data analysis was performed from August 2020 to July 2021. Exposures: Cardiac mitoKATP channel high-affinity (glyburide and glipizide) and low-affinity (gliclazide and glimepiride) sulfonylureas combined with metformin. Main Outcomes and Measures: Primary outcome was major adverse cardiovascular events (MACEs), a composite of cardiovascular death or hospitalization for either MI or ischemic stroke. Secondary outcomes included individual MACE components, heart failure, arrhythmia, all-cause mortality, and severe hypoglycemia. Cox proportional hazards models were used to estimate adjusted hazard ratios (aHRs). Results: Each sulfonylurea group comprised 53 714 patients (mean [SD] age, 54.7 [12.1] years; 31 962 men [59.5%]). MitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas when combined with metformin were associated with an increased risk of MACE (aHR, 1.18; 95% CI, 1.03-1.34), MI (aHR, 1.34; 95% CI, 1.04-1.73), all-cause mortality (aHR, 1.27; 95% CI, 1.03-1.57), and severe hypoglycemia (aHR, 1.82; 95% CI, 1.58-2.10), but not with increased risks of ischemic stroke, cardiovascular death, arrhythmia, and heart failure. The duration analyses revealed the highest MACE risk during 1 to 90 days after initiation of mitoKATP channel high-affinity sulfonylureas (aHR, 6.06; 95% CI, 4.86-7.55). Conclusions and Relevance: Use of mitoKATP channel high-affinity sulfonylureas vs low-affinity sulfonylureas was associated with an increased MACE risk in patients with T2D concomitantly receiving metformin, suggesting that high-affinity blockage of the mitoKATP channels could account for sulfonylurea-associated MACEs.

Functional characterization of a terpene synthase responsible for (E)-ß-ocimene biosynthesis identified in Pyrus betuleafolia transcriptome after herbivory.

(E)-ß-ocimene, a ubiquitous monoterpene volatile in plants, is emitted from flowers to attract pollinators and/or from vegetative tissues as part of inducible defenses mediated by complex signaling networks when plants are attacked by insect herbivores. Wild pear species Pyrus betuleafolia used worldwide as rootstock generally displays valuable pest-resistant traits and is a promising genetic resource for pear breeding. In the current study, transcriptional changes in this wild pear species infested with a polyphagous herbivore Spodoptera litura and the underlying molecular mechanisms were fully investigated. A total of 3,118 differentially expressed genes (DEGs) were identified in damaged pear leaf samples. Spodoptera litura larvae infestation activated complex phytohormonal signaling networks in which jasmonic acid, ethylene, brassinosteroids, cytokinin, gibberellic acid and auxin pathways were induced, whereas salicylic acid and abscisic acid pathways were suppressed. All DEGs associated with growth-related photosynthesis were significantly downregulated, whereas most DEGs involved in defense-related early signaling events, transcription factors, green leaf volatiles and volatile terpenes were significantly upregulated. The PbeOCS (GWHGAAYT028729), a putative (E)-ß-ocimene synthase gene, was newly identified in P. betuleafolia transcriptome. The upregulation of PbeOCS in S. litura-infested pear leaves supports a potential role for PbeOCS in herbivore-induced plant defenses. In enzyme-catalyzed reaction, recombinant PbeOCS utilized only geranyl pyrophosphate but not neryl diphosphate, farnesyl pyrophosphate or geranylgeranyl diphosphate as a substrate, producing (E)-ß-ocimene as the major product and a trace amount of (Z)-ß-ocimene. Moreover, as a catalytic product of PbeOCS, (E)-ß-ocimene showed repellent effects on larvae of S. litura in dual-choice bioassays. What is more, (E)-ß-ocimene increased mortalities of larvae in no-choice bioassays. These findings provide an overview of transcriptomic changes in wild pears in response to chewing herbivores and insights into (E)-ß-ocimene biosynthesis in pear plants, which will help elucidate the molecular mechanisms underlying pear-insect interactions.

HER2 status of CTCs by peptide-functionalized nanoparticles as the diagnostic biomarker of breast cancer and predicting the efficacy of anti-HER2 treatment.

Efficacy of anti-human epidermal growth factor receptor 2 (HER2) treatment is impacted by tissue-based evaluation bias due to tumor heterogeneity and dynamic changes of HER2 in breast cancer. Circulating tumor cell (CTC)-based HER2 phenotyping provides integral and real-time assessment, benefiting accurate HER2 diagnosis. This study developed a semi-quantitative fluorescent evaluation system of HER2 immunostaining on CTCs by peptide-functionalized magnetic nanoparticles (Pep@MNPs) and immunocytochemistry (ICC). 52 newly-diagnosed advanced breast cancer patients were enrolled for blood samples before and/or after first-line treatment, including 24 patients who were diagnosed with HER2+ tumors and treated with anti-HER2 drugs. We enumerated CTCs and assessed levels of HER2 expression on CTCs in 2.0 ml whole blood. Enumerating CTCs at baseline could distinguish cancer patients (sensitivity, 69.2%; specificity, 100%). 80.8% (42/52) of patients had at least one CTCs before therapy. Patients with <3 CTCs at baseline had significantly longer progression-free survival (medians, 19.4 vs. 9.2 months; log-rank p = 0.046) and overall survival (medians, not yet reached; log-rank p = 0.049) than those with ≥3 CTCs. Both HER2+ and HER2-low patients could be detected with HER2 overexpression on CTCs (CTC-HER2+) (52.6%, 44.4%, respectively), whereas all the HER2-negative patients had no CTC-HER2+ phenotype. Among HER2+ patients with ≥3 CTCs at baseline, objective response only appeared in pretherapeutic CTC-HER2+ cohort (60.0%), rather than in CTC-HER2- cohort (0.0%) (p = 0.034). In conclusion, we demonstrate the significance of CTC enumeration in diagnosis and prognosis of first-line advanced breast cancer, and highlight the value of CTC-HER2 status in predicting efficacy of anti-HER2 treatment.