Synthesis of substituted terpyridine nickel nitrate complexes and their inhibitory selectivity against cancer cell lines.

Six terpyridine­nickel complexes 1-6 were formed by the coordination of 4'-(4-R-phenyl)-2,2':6',2″-terpyridine (R = hydroxyl (L1), methoxyl (L2), methylsulfonyl (L3), fluoro (L4), bromo (L5), iodo (L6)) derivatives to nickel nitrate. The compositions and structures of these complexes were analyzed by Fourier Transform infrared spectroscopy (FT-IR), elemental analyses, electrospray ionization mass spectra (ESI-MS), solid-state ultraviolet-visible (UV-Vis) spectroscopy, and single crystal X-ray diffraction (1, 2 and 4) studies. In vitro anticancer cell proliferation experiments against SiHa (human cervical squamous cancer cell line) cells, Bel-7402 (human hepatoma cancer cell line), Eca-109 (human esophageal cancer cell line) and HL-7702 (human normal hepatocyte cell line) indicate that they have more excellent anti-proliferation effects than the cis-platin against Siha cells, Bel-7402 cells and Eca-109 cells. Especially, complex 5 showed a rather outstanding inhibitory effect against the SiHa cell line and was less toxic than the other compounds to the HL-7702 cell line, implying an obvious specific inhibitory effect. Therefore, complex 5 has the potential value to be developed as an anticancer cell-specific drug against human cervical squamous carcinoma. Molecular docking simulation, UV-vis absorption spectroscopy and circular dichroism experiments show that they prefer to bind to DNA part in an embedded binding manner.

IGF2BP2-related modification patterns in pancreatic cancer: A machine learning-driven approach towards personalized treatment.

Pancreatic cancer (PC) is a malignant digestive system tumor with a very poor prognosis. N6-methyladenosine (m6A) is mediated by a variety of readers and participates in important regulatory roles in PC. Based on TCGA_PAAD, ICGC_AU_PAAD, ICGC_CA_PAAD, GSE28735 and GSE62452 datasets, We mapped the multi-omics changes of m6A readers in PC and found that m6A readers, especially IGF2BP family genes, had specific changes and were significantly associated with poor prognosis. An unsupervised consensus clustering algorithm was used to explore the correlation between specific expression patterns of m6A readers in PC and enrichment pathways, tumor immunity and clinical molecular subtypes. Then, the principal component analysis (PCA) algorithm was used to quantify specific expression patterns and screen core genes. Machine learning algorithms such as Bootstrapping and RSF were used to quantify the expression patterns of core genes and construct a prognostic scoring model for PC patients. What's more, pharmacogenomic databases were used to screen sensitive drug targets and small molecule compounds for high-risk PC patients in an all-around and multi-angle way. Our study has not only provided new insights into personalized prognostication approaches, but also thrown light on integrating tailored risk stratification with precision therapy based on IGF2BP2-mediated m6A modification patterns.

NRG1-ErbB4 signaling in the medial amygdala controls mating motivation in adult male mice.

Motivation-driven mating is a basic affair for the maintenance of species. However, the underlying molecular mechanisms that control mating motivation are not fully understood. Here, we report that NRG1-ErbB4 signaling in the medial amygdala (MeA) is pivotal in regulating mating motivation. NRG1 expression in the MeA negatively correlates with the mating motivation levels in adult male mice. Local injection and knockdown of MeA NRG1 reduce and promote mating motivation, respectively. Consistently, knockdown of MeA ErbB4, a major receptor for NRG1, and genetic inactivation of its kinase both promote mating motivation. ErbB4 deletion decreases neuronal excitability, whereas chemogenetic manipulations of ErbB4-positive neuronal activities bidirectionally modulate mating motivation. We also identify that the effects of NRG1-ErbB4 signaling on neuronal excitability and mating motivation rely on hyperpolarization-activated cyclic nucleotide-gated channel 3. This study reveals a critical molecular mechanism for regulating mating motivation in adult male mice.

Mediating effect of inflammation on the relationship between sleep disruption and suicidal ideation in major depressive disorder.

BACKGROUND: Sleep disruption, particularly insomnia, is a notable characteristic of depression and is associated with an increased risk of suicide in patients diagnosed with major depressive disorder (MDD). Moreover, the pathophysiology of depression and suicide has been linked to inflammation, specifically proinflammatory cytokines. However, the complex interplay among these factors in individuals with MDD remains poorly understood. This study investigated the mediating role of inflammatory cytokines in the relationship between sleep disruption and suicidal ideation (SI), with a particular emphasis on gender differences. METHODS: This study used a cross-sectional design in which 281 individuals diagnosed with MDD were recruited from psychiatric clinics. The main assessments included the evaluation of sleep disruption, inflammatory markers, and SI. The Beck Scale for Suicide Ideation (SSI) scores was employed to quantify SI, whereas HAMD-SLD, a component of the Hamilton Rating Scale (HAMD-17), was used to evaluate sleep disruption. Blood analysis was performed to measure inflammatory markers. RESULT: For females diagnosed with MDD, significant associations between sleep disruption and the levels of IL-6 (B = 0.994, p = 0.013) and TNF-α (B = 1.986, p = 0.016) were found when IL-6 or TNF-α were considered as mediators in the regression model. In addition, IL-6 (B = 5.689, p < 0.001) and TNF-α (B = 9.916, p = 0.006) exhibited strong correlation with SSI scores. CONCLUSIONS: The primary results of this study indicate that IL-6 and TNF-α could function as potential mediators in the relationship between sleep disruption and SI among female patients diagnosed with MDD. CLINICAL TRIAL: Name of the registry: Zhejiang University Trial registration number: ChiCTR1800017626 Date of registration: 2018-08-07, 'Retrospectively registered' URL of trial registry record: https://www.chictr.org.cn/showproj.html?proj=27321.

A loss-of-function variant in ZCWPW1 causes human male infertility with sperm head defect and high DNA fragmentation.

BACKGROUND: Male infertility is a global health issue. The more causative genes related to human male infertility should be further explored. The essential role of Zcwpw1 in male mouse fertility has been established and the role of ZCWPW1 in human reproduction needs further investigation to verify. METHODS: An infertile man with oligoasthenoteratozoospermia phenotype and his parents were recruited from West China Second University Hospital, Sichuan University. A total of 200 healthy Han Chinese volunteers without any evidence of infertility were recruited as normal controls, while an additional 150 infertile individuals were included to assess the prevalence of ZCWPW1 variants in a sporadic male sterile population. The causative gene variant was identified by Whole-exome sequencing and Sanger sequencing. The phenotype of the oligoasthenoteratozoospermia was determined by Papanicolaou staining, immunofluorescence staining and electron microscope. In-vitro experiments, western blot and in-silicon analysis were applied to assess the pathogenicity of the identified variant. Additionally, we examined the influence of the variant on the DNA fragmentation and DNA repair capability by Sperm Chromatin Dispersion and Neutral Comet Assay. RESULTS: The proband exhibits a phenotype of oligoasthenoteratozoospermia, his spermatozoa show head defects by semen examination, Papanicolaou staining and electron microscope assays. Whole-exome sequencing and Sanger sequencing found the proband carries a homozygous ZCWPW1 variant (c.1064C > T, p. P355L). Immunofluorescence analysis shows a significant decrease in ZCWPW1 expression in the proband's sperm. By exogenous expression with ZCWPW1 mutant plasmid in vitro, the obvious declined expression of ZCWPW1 with the mutation is validated in HEK293T. After being treated by hydroxyurea, MUT-ZCWPW1 transfected cells and empty vector transfected cells have a higher level of γ-H2AX, increased tail DNA and reduced H3K9ac level than WT-ZCWPW1 transfected cells. Furthermore, the Sperm Chromatin Dispersion assay revealed the proband's spermatozoa have high DNA fragmentation. CONCLUSIONS: It is the first report that a novel homozygous missense mutation in ZCWPW1 caused human male infertility with sperm head defects and high DNA fragmentation. This finding enriches the gene variant spectrum and etiology of oligoasthenoteratozoospermia.

Machine learning algorithm integrates bulk and single-cell transcriptome sequencing to reveal immune-related personalized therapy prediction features for pancreatic cancer.

Pancreatic cancer (PC) is a digestive malignancy with worse overall survival. Tumor immune environment (TIME) alters the progression and proliferation of various solid tumors. Hence, we aimed to detect the TIME-related classifier to facilitate the personalized treatment of PC. Based on the 1612 immune-related genes (IRGs), we classified patients into Immune_rich and Immune_desert subgroups via consensus clustering. Patients in distinct subtypes exhibited a difference in sensitivity to immune checkpoint blockers (ICB). Next, the immune-related signature (IRS) model was established based on 8 IRGs (SYT12, TNNT1, TRIM46, SMPD3, ANLN, AFF3, CXCL9 and RP1L1) and validated its predictive efficiency in multiple cohorts. RT-qPCR experiments demonstrated the differential expression of 8 IRGs between tumor and normal cell lines. Patients who gained lower IRS score tended to be more sensitive to chemotherapy and immunotherapy, and obtained better overall survival compared to those with higher IRS scores. Moreover, scRNA-seq analysis revealed that fibroblast and ductal cells might affect malignant tumor cells via MIF-(CD74+CD44) and SPP1-CD44 axis. Eventually, we identified eight therapeutic targets and one agent for IRS high patients. Our study screened out the specific regulation pattern of TIME in PC, and shed light on the precise treatment of PC.

The core inflammatory factors in patients with major depressive disorder: a network analysis.

Introduction: The symptoms of major depressive disorder (MDD) vary widely. Psycho-neuro-inflammation has shown that MDD's inflammatory factors can accelerate or slow disease progression. This network analysis study examined the complex interactions between depressed symptoms and inflammatory factors in MDD prevention and treatment. Measures: We gathered participants' inflammatory factor levels, used the Hamilton Depression Scale (HAMD-17), and network analysis was used to analyzed the data. Network analysis revealed the core inflammatory (nodes) and their interactions (edges). Stability and accuracy tests assessed these centrality measures' network robustness. Cluster analysis was used to group persons with similar dimension depressive symptoms and examine their networks. Results: Interleukin-1ß (IL-1ß) is the core inflammatory factor in the overall sample, and IL-1ß-interleukin-4 (IL-4) is the strongest correlation. Network precision and stability passed. Network analysis showed significant differences between Cluster 1 (with more severe anxiety/somatization and sleep disruption) and Cluster 3 (with more severe retardation and cognitive disorders), as well as between Cluster 2 (with more severe anxiety/somatization, sleep disruption and body weight) and Cluster 3. IL-1ß is the core inflammatory factor in Cluster 1 and Cluster 2, while tumor necrosis factor alpha (TNF-α) in Cluster 3. Conclusion: IL-1ß is the central inflammatory factor in the network, and there is heterogeneity in the core inflammatory factor of MDD with specific depressive dimension symptoms as the main manifestation. In conclusion, inflammatory factors and their links should be prioritized in future theoretical models of MDD and may provide new research targets for MDD intervention and treatment.

Nickel chloride complexes with substituted 4'-phenyl-2',2':6',2″-terpyridine ligands: synthesis, characterization, anti-proliferation activity and biomolecule interactions.

A series of Ni(II) sandwich-like coordinated compounds were synthesized by the reaction of nickel dichloride and ten 4'-(4-substituent phenyl)-2',2':6',2″-terpyridine ligands, and their structures were confirmed by elemental analysis, FT-IR, ESI-MS, solid state ultraviolet spectroscopy and X-ray single crystal diffraction analysis. Three human cancer cell lines and a normal human cell line were used for anti-proliferation potential study: human lung cancer cell line (A549), human esophageal cancer cell line (Eca-109), human liver cancer cells (Bel-7402) and normal human liver cells (HL-7702). The results show that these nickel complexes possess good inhibitory effects on the cancer cells, outperforming the commonly used clinical chemotherapy drug cisplatin. Especially, complexes 3 (-methoxyl) and 7 (-fluoro) have strong inhibitory ability against Eca-109 cell line with IC50 values of 0.223 µM and 0.335 µM, complexes 4 and 6 showed certain cell selectivity, and complex 6 can inhibit cancer cells and slightly poison normal cells when the concentration was controlled. The ability of these complexes binding to CT-DNA was studied by UV titration and CD spectroscopy, and CD spectroscopy was also used to study the secondary structural change of BSA under the action of the complexes. The binding of these complexes with DNA, DNA-Topo I and bovine serum protein has been simulated by molecular docking software, and the docking results and optimal binding conformation data showed that they interacted with DNA in the mode of embedded binding, which is consistent with the experimental results. These complexes are more inclined to move to the cleavage site when docking with DNA-Topo I, so as to play a role of enzyme cleavage, while BSA promotes the action of the complexes by binding to effective binding sites.

Massage therapy significantly improves cancer-related fatigue in cancer patients: a meta-analysis of randomized controlled trials.

PURPOSE: This study was designed to investigate the effectiveness and safety of massage therapy in cancer-related fatigue (CRF) and to provide a reference for the future management of CRF. METHODS: Eight databases (PubMed, Embase, Cochrane Library, CINAHL, Sinomed, Chinese Scientific Journal database (VIP), Wanfang, and China National Knowledge Infrastructure (CNKI)) were systematically reviewed from inception to May 2022 for randomized controlled trials. Two reviewers critically and independently assessed the risk of bias using Cochrane Collaboration criteria and extracted correlated data using the designed form. The meta-analysis was performed using RevMan 5.3 to calculate the pooled effect sizes and 95% confidence intervals (CIs). Sensitivity analysis was performed to find the source of the heterogeneity. Publication bias was assessed via funnel plot analysis and the Egger test. RESULT: A total of 11 qualified studies that included 789 patients (massage therapy group: 389; control group: 400) were included in the meta-analysis. Massage therapy had a marked effect on fatigue in cancer patients [standardized mean difference (SMD) = - 1.69, 95% CI (- 2.46, - 0.93), P < 0.01], especially in breast cancer [SMD = - 1.62, 95% CI (- 2.18, - 1.05), P < 0.01]. Reflexology [SMD = - 2.71, 95% CI (- 4.65, - 0.77), P < 0.01] and Chinese massage [SMD = - 1.14, 95% CI (- 1.95, - 0.33), P < 0.01] can have a more significant effect on fatigue. Massage time is 20 to 40 min [SMD = - 2.39, 95% CI (- 4.13, - 0.66), P < 0.01], twice a week [SMD = - 3.46, 95% CI (- 5.47, - 1.45), P < 0.01] for 3-5 weeks [SMD = - 2.36, 95% CI (- 3.53, - 1.19), P < 0.01], which is more effective in relieving fatigue in cancer patients. Five studies described the occurrence of adverse events and only two studies had adverse events. CONCLUSION: Massage therapy can be effective in relieving fatigue in cancer patients. Current evidence suggests that reflexology is the most effective approach to relieve fatigue, particularly in the breast cancer patients. The optimal intervention frequency and cycle for massage therapy is twice a week for 3-5 weeks, and the optimal duration is 20-40 min.

Silicate Nanoplatelets Promotes Neuronal Differentiation of Neural Stem Cells and Restoration of Spinal Cord Injury.

Neural stem cell (NSC) transplantation has been suggested as a promising therapeutic strategy to replace lost neurons after spinal cord injury (SCI). However, the low survival rate and neuronal differentiation efficiency of implanted NSCs within the lesion cavity limit the application. Furthermore, it is difficult for transplanted cells to form connections with host cells. Thus, effective and feasible methods to enhance the efficacy of cell transplantation are needed. In this study, the effect of Laponite nanoplatelets, a type of silicate nanoplatelets, on stem cell therapy is explored. Laponite nanoplatelets can induce the neuronal differentiation of NSCs in vitro within five days, and RNA sequencing and protein expression analysis demonstrated that the NF-κB pathway is involved in this process. Moreover, histological results revealed that Laponite nanoplatelets can increase the survival rate of transplanted NSCs and promote NSCs to differentiate into mature neurons. Finally, the formation of connections between transplanted cells and host cells is confirmed by axon tracing. Hence, Laponite nanoplatelets, which drove neuronal differentiation and the maturation of NSCs both in vitro and in vivo, can be considered a convenient and practical biomaterial to promote repair of the injured spinal cord by enhancing the efficacy of NSC transplantation.

A comparative analysis of antidepressant and anti-suicidal effects of repeated ketamine infusions in elderly and younger adults with depression.

OBJECTIVES: This study aims to investigate the differences in safety and antidepressant effects of multi-infusion ketamine treatment between elderly and young adults with depression. METHODS: The safety, antidepressant, and anti-suicidal effects of multi-infusion ketamine were compared between 19 elderly (≥50 years) and 116 younger (<50 years) adults with depression; all were treated with six ketamine infusions (0.5 mg/kg). Montgomery-Åsberg Depression Rating Scale (MADRS) was used to measure the depressive symptoms, and suicidal ideation was measured with Beck Scale for Suicide Ideation (SSI)-part 1, Hamilton Rating Scale for Depression (HAMD) item 3, and (MADRS) item 10. Dissociative and psychotomimetic symptoms were evaluated based on the Clinician-Administered Dissociative States Scale (CADSS) and the Brief Psychiatric Rating Scale (BPRS)-four items. RESULTS: Multi-Ketamine infusions resulted in a lower (trend) antidepressant response (37.1 % versus 57.8 %) and antidepressant remission (15.8 % versus 47.4 %) in elderly patients with depression compared with younger patients with depression (all ps > 0.05). Interestingly, elderly patients with depression had a higher MADRS score after six ketamine infusions compared with younger patients (p = 0.04). No significant differences in SSI-part 1 scores, HAMD item 3 scores, MADRS item 10 scores, CADSS scores, and BPRS-four items scores were found between the two groups at any assessment point (all ps > 0.05). CONCLUSION: Our study shows that repeated-dose infusions of ketamine may be a feasible treatment strategy in elderly Chinese patients with depression; however, elderly patients with depression may be less responsive to ketamine compared with younger adults with depression.

AhR Promotes the Development of Non-small cell lung cancer by Inducing SLC7A11-dependent Antioxidant Function.

Objective: Aryl hydrocarbon receptor (AhR) is a transcription factor. It is reported that AhR is associated with non-small cell lung cancer (NSCLC), but the mechanisms underlying this relationship remain unclear. Therefore, we investigated the role of AhR in NSCLC to elucidate the underlying mechanisms. Methods: We collected clinical lung cancer samples and constructed AhR overexpression and knockdown cell lines to investigate the tumorigenicity of AhR in vivo and in vitro. Furthermore, we performed a ferroptosis induction experiment and chromatin immunoprecipitation experiment. Results: AhR was highly expressed in NSCLC tissue. AhR knockdown cells showed ferroptosis related phenomenon. Furthermore, Chromatin immunoprecipitation confirmed the correlation between AhR and solute carrier family 7 member 11 (SLC7A11) and ferroptosis induction experiment confirmed that AhR affects ferroptosis via SLC7A11. Specifically, AhR regulates ferroptosis-related SLC7A11, which affects ferroptosis and promotes NSCLC progression. Conclusions: AhR promoted NSCLC development and positively correlated with SLC7A11, affecting its actions. AhR bound to the promoter region of SLC7A11 promotes NSCLC by activating SLC7A11 expression, improving the oxidative sensitivity of cells, and inhibiting ferroptosis. Thus, AhR affects ferroptosis in NSCLC by regulating SLC7A11, providing foundational evidence for novel ferroptosis-related treatments.

HOXC11 drives lung adenocarcinoma progression through transcriptional regulation of SPHK1.

Lung adenocarcinoma (LUAD) is a fatal threat to human health, while the mechanism remains unclear, and the therapy brings limited therapeutic effects. Transcription factor Homeobox C11 (HOXC11) was previously proved to be related to hind limbs and metanephric development during the embryonic phase, and its role in tumors has been gradually recognized. Our study found that HOXC11 overexpressed in LUAD and was associated with worse overall survival. Moreover, its expression in lung cancer was regulated by IκB kinase α (IKKα), a pivotal kinase in NF-κB signaling, which was related to the ubiquitination of HOXC11. We further proved that HOXC11 could enhance the ability of proliferation, migration, invasion, colony formation, and the progression of the cell cycle in LUAD cells. Meanwhile, it also accelerated the formation of subcutaneous and lung metastases tumors. In contrast, loss of HOXC11 in LUAD cells significantly inhibited these malignant phenotypes. At the same time, HOXC11 regulated the expression of sphingosine kinase 1 (SPHK1) by directly binding to its promoter region. Therefore, we conclude that HOXC11 impacts the development of LUAD and facilitates lung cancer progression by promoting the expression of SPHK1.

Electroacupuncture modulates gut microbiota in mice: A potential target in postoperative cognitive dysfunction.

The detailed mechanism of inflammation in postoperative cognitive dysfunction (POCD) is unclear. This study aimed to determine whether electroacupuncture (EA) ameliorates POCD by modulating gut microbial dysbiosis. Compared to the control group, mice in the EA group were treated at the acupoints Zusanli (ST36), Quchi (L111), Baihui (GV20), and Dazhui (GV14) 1 week before appendectomy. Novel object recognition and the Morris water maze tests were used to assess learning and spatial reference memory deficits, whereas hippocampus samples and stool samples were collected for central inflammatory tests and 16S-rRNA sequencing of intestinal flora, respectively. In amyloid precursor protein/presenilin 1 (APP/PS1) mice, EA enhanced spatial memory and learning deficits. The fecal microbial community was altered in APP/PS1 mice in the absence of EA following surgery. Among them, Coprococcus and Bacteroidetes were more abundant in the EA groups than in the control groups; however, Actinobacteriota, Helicobacteraceae, and Escherichia/shigella constitute the minor bacterial colonization in the EA groups. Furthermore, we found a significant negative correlation between Firmicutes and escape latency (Pearson correlation coefficient - 0.551, p < 0.01) and positive correlation between Proteobacteria and escape latency (Pearson correlation coefficient 0.462, p < 0.05). Electron microscopy revealed signs of blood-brain barrier (BBB) impairments and immunofluorescence images showed glial cells activated in the hippocampus of APP/PS mice without EA, and serum diamine oxidase levels were increased in these mice; whereas EA treatment significantly relieved the above pathological changes. Our findings implied that EA decreases hippocampal inflammation of APP/PS1 by upregulating benificial  gut microbiota, reducing BBB and intestinal barrier dysfunction, thus alleviates postoperative cognitive dysfunction. This may provide a novel target in POCD management.

Biophilic virtual reality on children's anxiety and pain during circumcision: A randomized controlled study.

INTRODUCTION: The aim of this study was to evaluate the effects of the biophilic virtual reality (BVR) method on children's pain and anxiety undergoing circumcision. MATERIALS AND METHODS: This randomized controlled study used a parallel trial design guided by the CONSORT checklist. A total of 106 children were included in the analysis. Intraoperative anxiety was assessed by using the simplified Chinese version of the modified Yale Preoperative Anxiety Scale (CmYPAS), Visual Analogue Scale (VAS), heart rate (HR), and Anxiety index (Ai). Intraoperative pain was assessed by using the Faces Pain Scale-Revised (FPS-R), and Pain index (Pi). The Pearson correlation analysis was used to analyze the relationship between Ai and the CmYPAS. The primary outcomes were CmYPAS, VAS, and FPS-R, which were analyzed using the Kruskal-Wallis test. RESULTS: Baseline variables were not significantly different between the BVR group (34 patients), the indoor virtual reality (IVR) group (36 patients), and the blank control group (36 patients). The CmYPAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (25.0[22.9-29.2], 22.9[22.9-29.2], 33.3[33.3-38.5] respectively; P < 0.001). The VAS scores during surgery were significantly lower in the BVR group and the IVR group versus the blank control group (5.0[3.0-7.0], 3.0[2.0-5.0], 6.0[5.0-8.8] respectively; P < 0.001). The FPS-R scores during surgery were significantly lower in the BVR group and IVR group versus the blank control group (2.0[1.8-4.2], 3.0[2.0-4.8], 5.5[5.0-8.0], respectively; P < 0.001). At removal of the foreskin, Pi were significantly lower in the BVR group and IVR group versus the blank control group (6.9[4.1], 7.7[3.3], 9.8[6.2] respectively; P = 0.033). The Ai scores at each time point were significantly lower in the BVR group and IVR group versus the control (P = 0.015, P = 0.006 respectively). The correlation analysis of Ai (at removal of the foreskin) and CmYPAS scores in children showed that the Pearson correlation coefficient was 0.194 (P = 0.046). DISCUSSION: This is the first RCT to investigate the effects of BVR in children undergoing circumcision. This study demonstrates a reduction in pediatric intraoperative pain and anxiety with the use of virtual reality (VR). CONCLUSION: Intraoperative VR may be an effective noninvasive modality for reducing pain and anxiety during circumcision. Pi and Ai might be used to assess subjective pain and anxiety in patients.

Electrochemical sensor for sweat monitoring / Sensor eletroquímico para monitoramento de suor / Sensor electroquímico para el control del sudor

ABSTRACT Introduction: Attention is given to developing electrochemical sensors for the rapid and real-time measurement of lactate levels. The synthesis of electrochemical sensors is based on an electrode modified with a nanocomposite. Objective: Analyze an electrochemical sensor's feasibility for sports monitoring sweat in lactate. The Au@CNTs were the main focus of this study. Methods: The Au@CNTs composite was synthesized on the GCE surface and tested under pre-established protocols as a sensor. Results: The shape and structure of the modified electrodes were analyzed using SEM. The results showed that the Au@CNTs nanoparticles in the Au@CNTs nanocomposite were evenly distributed throughout the porous CNTs network. The performance of the developed sensor was measured using cyclic voltammetry and amperometry. The electrochemical biosensor responded linearly to lactate over phosphate buffer solution with a low detection limit and sensitivity. Conclusion: The experiment of this sensor evaluated lactate concentrations in real sweat samples that were exceptionally close to the injection amount, enabling it as an effective biosensor for the detection of lactate in sweat samples. Level of Evidence: Therapeutic Studies - Outcome Investigation.

RESUMO Introdução: É dada atenção ao desenvolvimento de sensores eletroquímicos para a medição rápida e em tempo real dos níveis de lactato. A síntese de sensores eletroquímicos é baseada em um eletrodo modificado com um nanocomposto. Objetivo: Analisar a viabilidade de um sensor eletroquímico para monitoramento esportivo de suor em lactato. O Au@CNTs foi o foco principal deste estudo. Métodos: O composto Au@CNTs foi sintetizado na superfície GCE, e testado sob protocolos preestabelecidos como sensor. Resultados: A forma e estrutura dos eletrodos modificados foram analisadas usando SEM, e os resultados mostraram que as nanopartículas de Au@CNTs no nanocomposto Au@CNTs foram distribuídas uniformemente por toda a rede porosa de CNTs. O desempenho do sensor desenvolvido foi medido usando voltametria cíclica e amperometria. O biosensor eletroquímico respondeu linearmente ao lactato sobre solução tampão fosfato com um limite de detecção e sensibilidade reduzidos. Conclusão: O experimento deste sensor avaliou as concentrações de lactato em amostras de suor real que estavam excepcionalmente próximas à quantidade de injeção, habilitando-o como um biosensor efetivo para detecção de lactato em amostras de suor. Nível de evidência: Estudos Terapêuticos - Investigação dos Resultados.

RESUMEN Introducción: Se presta atención al desarrollo de sensores electroquímicos para la medición rápida y en tiempo real de los niveles de lactato. La síntesis de los sensores electroquímicos se basa en un electrodo modificado con un nanocompuesto. Objetivo: Analizar la viabilidad de un sensor electroquímico para la monitorización esporádica del sudor en el lactato. Los Au@CNTs fueron el objetivo principal de este estudio. Métodos: El compuesto de Au@CNTs se sintetizó sobre la superficie de GCE, y se probó bajo protocolos preestablecidos como sensor. Resultados: La forma y la estructura de los electrodos modificados se analizaron mediante SEM, y los resultados mostraron que las nanopartículas de Au@CNTs en el nanocompuesto de Au@CNTs estaban distribuidas uniformemente en la red porosa de CNTs. El rendimiento del sensor desarrollado se midió mediante voltamperometría cíclica y amperometría. El biosensor electroquímico respondió linealmente al lactato sobre la solución tampón de fosfato con un bajo límite de detección y sensibilidad. Conclusión: El experimento de este sensor evaluó las concentraciones de lactato en muestras reales de sudor que eran excepcionalmente cercanas a la cantidad inyectada, lo que le permite ser un biosensor eficaz para la detección de lactato en muestras de sudor. Nivel de evidencia: Estudios terapéuticos - Investigación de resultados.

Clinical Effect of Fuzheng Guben Decoction in the Treatment of Localized Prostate Cancer and Its Influence on Immune Function under Continuous Nursing Intervention.

In order to explore the clinical effect and immune function of patients with localized prostate cancer combined with continuous nursing intervention and Fuzheng Guben decoction, a total of 72 patients with prostate cancer admitted to our hospital from January 2020 to June 2021 are selected and analyzed. The patients are randomly divided into a study group and control group randomly, and the control group and the research group are treated with routine intervention and chemotherapy, continuous nursing intervention, and Fuzheng Guben decoction on the basis of chemotherapy, respectively. The incidence of postoperative urinary incontinence and other complications between the two groups are counted, and the differences of FHIT, CatD, CatL, CD68, and CD83 levels in the patients are compared. Furthermore, the total treatment response rate and self-attitude score of the two groups are compared after treatment. The experimental results demonstrate that the total effective rate and self-attitude score of patients in the study group are significantly better than those in the control group.

The vitamin e consumption effect on muscle damage and oxidative stress: a systematic review and meta-analysis of randomized controlled trials / Efeito da ingestão de vitamina e sobre os danos musculares e o estresse oxidativo: uma revisão sistemática com meta-análise de ensaios controlados randomizados / Efecto del consumo de vitamina e sobre el daño muscular y el estrés oxidativo: una revisión sistemática con metaanálisis de ensayos controlados aleatorios

ABSTRACT Introduction: Vitamin E supplementation may protect against exercise-induced muscle damage (EIMD) through possible inhibition of free radical formation and cell membrane stabilization. However, there is no systematic review of this topic. This fact maintains academic stalemates that may have a resolution. Objective: This systematic review with meta-analysis aims to provide a comprehensive literature review on the hypothesis of the benefit of vitamin E supplementation on oxidative stress and muscle damage induced by aerobic exercise. Methods: A random-effects model was used, weighted mean difference (WMD) and 95% confidence interval (CI) were applied to estimate the overall effect. Results: The results revealed a significant effect of vitamin E supplementation on reducing creatine kinase (CK) and lactate dehydrogenase (LDH). In addition, a subgroup analysis resulted in a significant decrease in CK concentrations in trials with immediate and <24 hours post-exercise CK measurement; <1000 at daily vitamin E intake; ≤1 at weekly intake; 1 at six weeks and >6 weeks experimental duration, studies on aerobic exercise and training were part of the crossover study. Conclusion: Vitamin E can be seen as a priority agent for recovery from muscle damage. Evidence Level II; Therapeutic Studies - Investigating the results.

RESUMO Introdução: A suplementação de vitamina E pode ter um efeito protetor contra danos musculares induzidos pelo exercício (EIMD) através da possível inibição da formação radical livre e estabilização da membrana celular. Todavia, não há uma revisão sistemática sobre esse tema. Tal fato mantém empasses acadêmicos que podem ter uma resolução. Objetivo: Esta revisão sistemática com meta-análise objetiva fornecer uma análise bibliográfica abrangente na hipótese do benefício na suplementação de vitaminas E sobre o estresse oxidativo e os danos musculares induzidos pelo pelo exercício aeróbico. Métodos: Foi utilizado um modelo com efeitos aleatórios, diferença média ponderada (ADM) e intervalo de confiança de 95% (IC) foram aplicados para estimar o efeito geral. Resultados: Os resultados revelaram um efeito significativo da suplementação de vitamina E na redução da creatina-quinase (CK) e lactato-desidrogenase (LDH). Além disso, uma análise do subgrupo resultou em uma diminuição significativa das concentrações de CK em ensaios com medição imediata e <24 horas de CK após o exercício; <1000 no consumo diário de vitamina E; ≤1 no consumo semanal; 1 em 6 semanas e >6 semanas de duração experimental, estudos sobre exercício aeróbico e treinamento fizeram parte do estudo cruzado. Conclusão: A vitamina E pode ser vista como um agente prioritário de recuperação de danos musculares. Nível de evidência II; Estudos Terapêuticos - Investigação de Resultados.

RESUMEN Introducción: La suplementación con vitamina E puede tener un efecto protector contra el daño muscular inducido por el ejercicio (EIMD) a través de la posible inhibición de la formación de radicales libres y la estabilización de la membrana celular. Sin embargo, no existe ninguna revisión sistemática sobre este tema. Este hecho mantiene un impasse académico que puede tener resolución. Objetivo: Esta revisión sistemática con meta-análisis tiene como objetivo proporcionar una amplia revisión de la literatura sobre la hipótesis del beneficio de la suplementación con vitamina E sobre el estrés oxidativo y el daño muscular inducido por el ejercicio aeróbico. Métodos: Se utilizó un modelo de efectos aleatorios, se aplicó la diferencia de medias ponderada (DMP) y el intervalo de confianza (IC) del 95% para estimar el efecto global. Resultados: Los resultados revelaron un efecto significativo de la suplementación con vitamina E en la reducción de la creatina quinasa (CK) y la lactato deshidrogenasa (LDH). Además, un análisis de subgrupos dio como resultado una disminución significativa de las concentraciones de CK en los ensayos con medición de CK inmediata y <24 horas después del ejercicio; <1000 en la ingesta diaria de vitamina E; ≤1 en la ingesta semanal; 1 en 6 semanas y >6 semanas de duración experimental, los estudios sobre el ejercicio aeróbico y el entrenamiento formaron parte del estudio cruzado. Conclusión: La vitamina E puede resultar un agente prioritario para la recuperación del daño muscular. Nivel de evidencia II; Estudios terapéuticos - Investigación de resultados.

Magnetic Resonance Imaging Guided Prostate Biopsy in Patients with ≥ One Negative Systematic Transrectal Ultrasound-Guided Biopsy: A Systemic Review and Meta-Analysis.

The present study aimed to compare prostate cancer (PCa) and clinically significant PCa (csPCa) detection sensitivity between magnetic resonance imaging guided-biopsy (MRI-GB) and transrectal ultrasound-guided biopsy (TRUS-GB) in patients with ≥ 1 negative TRUS-GB, and to explore the additive value of TRUS-GB to MRI-GB. The meta-analysis of 18 studies demonstrated that MRI-GB had a similar sensitivity for PCa detection but a higher sensitivity for csPCa than TRUS-GB. In conclusion, there was limited value in combining TRUS-GB with MRI-GB compared with MRI-GB alone for csPCa detection in patients with one or more negative TRUS-GBs that were suspicious of having PCa.

Identification of senescence-related subtypes, establishment of a prognosis model, and characterization of a tumor microenvironment infiltration in breast cancer.

Breast cancer is a malignancy with the highest incidence and mortality in women worldwide. Senescence is a model of arrest in the cell cycle, which plays an important role in tumor progression, while the prognostic value of cellular senescence-related genes (SRGs) in evaluating immune infiltration and clinical outcomes of breast cancer needs further investigation. In the present study, we identified two distinct molecular subtypes according to the expression profiles of 278 SRGs. We further explored the dysregulated pathways between the two subtypes and constructed a microenvironmental landscape of breast cancer. Subsequently, we established a senescence-related scoring signature based on the expression of four SRGs in the training set (GSE21653) and validated its accuracy in two validation sets (GSE20685 and GSE25055). In the training set, patients in the high-risk group had a worse prognosis than patients in the low-risk group. Multivariate Cox regression analysis showed that risk score was an independent prognostic indicator. Receiver operating characteristic curve (ROC) analysis proved the predictive accuracy of the signature. The prognostic value of this signature was further confirmed in the validation sets. We also observed that a lower risk score was associated with a higher pathological response rate in patients with neoadjuvant chemotherapy. We next performed functional experiments to validate the results above. Our study demonstrated that these cellular senescence patterns effectively grouped patients at low or high risk of disease recurrence and revealed their potential roles in the tumor-immune-stromal microenvironment. These findings enhanced our understanding of the tumor immune microenvironment and provided new insights for improving the prognosis of breast cancer patients.