In vitro anticancer study of novel curcumin derivatives via targeting PI3K/Akt/p53 signaling pathway.

Four new series of curcumin derivatives bearing NO-donating moiety were synthesized via etherification, nucleophilic substitution, and Knoevenagel condensation etc. The cytotoxicity activity of curcumin derivatives against five human tumor cell lines (A549, Hela, HepG2, MCF-7 and HT-29) and two normal cell lines (LO-2 and HK-2) has been studied. The results showed that compound 6a could inhibit the proliferation of MCF-7 cells remarkably and exhibit low toxicity to normal cells. Also, the underlying mechanism in vitro of compound 6a on MCF-7 was investigated. It has been found that compound 6a induced G2/M arrest and apoptosis of MCF-7 in a dose-dependent manner. Compound 6a-induced the fluorescence changes of ROS in MCF-7 cells confirmed the occurrence of apoptosis. Western Blot suggested that compound 6a decreased the expression of PI3K, as well as increased the expression of p53, cleaved caspase-9 and cleaved caspase-3. Furthermore, molecular docking revealed that compound 6a could bind well at active site of PI3K (3zim) with total score 9.59. Together, compound 6a, a potential PI3K inhibitor, may inhibit the survival of MCF-7 cells via interfering with PI3K/Akt/p53 pathway.

Effects of different plasma treatments on bonding properties of zirconia.

This in vitro study was to evaluate the effect of different non-thermal atmospheric pressure plasma (NTP) on shear bond strength (SBS) between yttria-stabilized tetragonal zirconia polycrystal (Y-TZP) and self-adhesive resin cement. In this study, The Y-TZP specimens were divided into 4 groups according to the surface treatment methods as follows: Control (no surface treatment), Sb (Sandblasting), AP(argon NTP), and CP(20 % oxygen and 80 % argon combination NTP). Y-TZP specimens were randomly selected from each group to observe and test the following indexes: scanning electron microscope to observe the surface morphology; atomic force microscope to detect the surface roughness; contact angle detector to detect the surface contact angle; energy spectrometer to analyze the surface elements. Then, resin cement (Rely X-U200) was bonded to human isolated teeth with Y-TZP specimens to measure SBS. The results showed that for the SE test, the NTP group was significantly higher than the control group (p < 0.05). The results of the SBS test showed that the SBS values of the NTP group were significantly higher than those of the other groups, regardless of the plasma treatment (p < 0.05). However, there was no significant difference between groups AP and CP in a test of SBS (p > 0.05). This study shows that non-thermal atmospheric pressure plasma can improve the shear bond strength of Y-TZP by increasing the surface energy. The addition of oxygen ratio to argon is more favorable to increase the shear bond strength and is worth further investigation.

Lycium barbarum polysaccharides regulate the gut microbiota to modulate metabolites in high-fat diet-induced obese rats.

Lycium Barbarum Polysaccharides (LBP) can benefit lipid parameters such as total cholesterol, triglyceride, and high-density lipoprotein levels and upregulate the level of Firmicutes, increase the diversity of gut microbiota and reduce metabolic disorders, finally relieving weight gain of obese rats. But it cannot reverse the outcome of obesity. Over 30 differential metabolites and four pathways are altered by LBP.

Correlation of imaging characteristics of degenerative cervical myelopathy and the surgical approach with improvement for postoperative neck pain and neural function: a retrospective cohort study.

Background: Complex degenerative cervical spondylotic myelopathy (DCM) is characterized by a variety of complex imaging features. The surgical method for DCM remains controversial. This study aimed to examine the correlation between the imaging characteristics of DCM with varying degrees of complexity and the surgical approach and clinical outcome. Methods: A retrospective cohort study involving retrospective data collection was performed. A total of 139 patients with DCM who underwent surgery between January 2015 and January 2018 in the Orthopedics Department of Shanxi Bethune Hospital were divided into 3 groups according to the complexity of imaging features: 18 patients in the mild group, 66 patients in the moderate group, and 55 patients in the severe group. The Visual Analog Scale (VAS) and Japanese Orthopaedic Association (JOA) scores were used to compare the effects of neck pain and neural function prior to surgery according to the rate of improvement as of the last follow-up. Routine X-ray films were obtained at the follow-up of 3-6 months. The necessity of computed tomography (CT) and magnetic resonance imaging (MRI) examinations was determined based on clinical findings and X-ray images. Analysis of variance (ANOVA) was used to compare groups, the least significant difference (LSD) test was used for multiple comparisons, and the Chi-square test was used to compare classification indicators (imaging manifestations, gender), with P<0.05 being statistically significant. Binary logistic regression analysis was performed to determine the primary influencing factors of the JOA recovery rate. Results: In all three groups, JOA and VAS scores at the final follow-up were significantly higher than those before surgery (P<0.001). There were significant differences in the preoperative VAS and JOA scores between any two groups, as well as in the VAS and JOA scores and improvement rates at the last follow-up between the mild group and the moderate group and between the mild group and the severe group (P<0.001). Age, preoperative JOA scores, MRI intramedullary hyperintensity signal, and the degree of spinal cord compression were primarily related to the nervous system recovery rate (P<0.001). Conclusions: Age, MRI intramedullary hyperintensity signal, degree of spinal cord compression, and other variables were associated with the improvement of neural function in patients with DCM. Therefore, in addition to the JOA improvement rate or VAS score, additional factors, such as the patient's condition, the improvement in quality of life, and the patient's financial capacity, should be considered in evaluating the improvement of postoperative neck pain and neural function.

Influences of Early Rehabilitation Nursing on Motor Function, Swallowing Function as Well as Quality of Life in Stroke Patients.

Background: Stroke is a major cause of long-term disability in adults. Routine nursing mainly meets the life needs of patients through the intervention of patients' general life but only provides the most basic services for patients, which makes it difficult to meet the requirements of patients' physical exercise and other aspects, affecting the prognosis. Early rehabilitation after a stroke is important for the recovery of bodily functions in stroke patients. However, the impacts of early rehabilitation nursing on motor function, swallowing function as well as quality of life in stroke patients remain to be further explored. Objective: To investigate the effects of early rehabilitation nursing on motor function, swallowing function as well as quality of life in stroke patients. Design: This was a randomized, single-blind, controlled experiment. Setting: This study was carried out in the neurology department at Xuzhou Central Hospital. Participants: A total of 116 acute stroke patients validated by craniocerebral computed tomography (CT) and magnetic resonance imaging (MRI) from January 2021 to December 2022 were chosen and separated into the control group (n=58) and research group (n=58) following the random number method. Interventions: The control group was given routine nursing. The research group implemented early rehabilitation nursing 24 hours after admission on the basis of the control group. Primary Outcome Measures: (1) recovery of swallowing dysfunction (2) recovery of limb function (3) self-care ability (4) sleep quality (5) quality of life and (6) total satisfaction of patients. Results: The research group had an elevated total effective rate of swallowing dysfunction recovery in contrast to the control group after nursing (P < .05). The recovery of limb function, self-care ability, sleep quality, and quality of life were promoted in both groups, followed by nursing (P < .05), and those in the research group were higher relative to the control group (P < .05). The total satisfaction of patients in the research group presented higher relative to the control group (P < .05). Conclusion: The application effect of early rehabilitation nursing in acute stroke patients is outstanding, and the swallowing dysfunction and limb dysfunction of patients can be effectively improved, which has a high nursing value and is worth promoting and applying. Therefore, an early physical rehabilitation program for acute stroke inpatients should be considered for implementation in clinical settings.

Enhanced stability and biocompatibility of HIPEs stabilized by cyclodextrin-metal organic frameworks with inclusion of resveratrol and soy protein isolate for ß-carotene delivery.

High internal phase Pickering emulsions (HIPEs) constitute a significant research domain within colloid interface chemistry, addressing the demand for robust emulsion systems across various applications. An innovative nanoparticle, synthesized from a cyclodextrin metal-organic framework encapsulated with a composite of resveratrol and soy isolate protein (RCS), was employed to fortify a high internal phase emulsion. The emulsion's three-dimensional printing capabilities, alongside the encapsulated delivery efficacy for ß-carotene, were thoroughly examined. Cyclodextrin metal-organic frameworks (CD-MOFs), facilitated by cellulose nanofibrils, were synthesized to yield particles at the nanoscale, maintaining a remarkable 97.67 % cellular viability at an elevated concentration of 1000 µg/ml. The RCS nanoparticles demonstrated thermal stability and antioxidant capacities surpassing those of CD-MOF. The integration of soybean isolate protein augmented both the hydrophobicity (from 21.95 ± 0.64° to 59.15 ± 0.78°) and the interfacial tension (from 14.36 ± 0.46 mN/m to 5.34 ± 0.81 mN/m) of the CD-MOF encapsulated with resveratrol, thereby enhancing the RCS nanoparticles' adsorption at the oil-water interface with greater stability. The durability of the RCS-stabilized high internal phase emulsions was contingent upon the RCS concentration. Emulsions stabilized with 5 wt%-RCS exhibited optimal physical and chemical robustness, demonstrating superior performance in emulsion 3D printing and ß-carotene encapsulation delivery. This investigation furnishes a novel perspective on the amalgamation of food customization and precision nutrition.

Effect of varying cuff sizes with identical inner diameter on endotracheal intubation in critically ill adults: A sealed tracheal controlled trial.

BACKGROUND: The present study aims to determine the impact of different cuff diameters on the cuff pressure of endotracheal tubes (ETTs) when the trachea is adequately sealed. METHODS: In the present single-center clinical trial, adult patients who underwent cardiothoracic surgery were assigned to use ETTs from 2 brands (GME and GZW). The primary endpoint comprised of the following: cuff diameter, inner diameter of the ETT, manufacturer, and the number of subjects with tracheal leakage when the cuff pressure was 30 cm H2O. RESULTS: A total of 298 patients were assigned into 2 groups, based on the 2 distinct brands of ETTs: experimental group (n = 122, GME brand) and control group (n = 176, GZW brand). There were no significant differences in baseline characteristics. However, the cuff diameter was significantly smaller in the control group, when compared to the experimental group (P = .001), and the incidence of tracheal leakage was significantly higher in the control group (P = .001). Furthermore, the GME brand ETT had a significantly larger cuff diameter, when compared to the GZW brand ETT. CONCLUSION: The cuff size would mismatch the tracheal area in clinical practice. Therefore, chest computed tomography is recommended to routinely evaluate the tracheal cross-sectional area during anesthesia, in order to ensure the appropriate cuff size selection.

Inhibiting the SARM1-NAD+ axis reduces oxidative stress-induced damage to retinal and nerve cells.

Retinal neurodegenerative diseases are a category of refractory blinding eye conditions closely associated with oxidative stress induced by mitochondrial dysfunction in retinal cells. SARM1, a core driver molecule leading to axonal degeneration, possesses NAD+ enzyme (NADase) activity. However, the role of the SARM1-NAD+ axis in oxidative stress-induced retinal cell death remains unclear. Here, we employed the SARM1 NADase inhibitor DSRM-3716 and established a glucose oxidase (GOx)-induced oxidative stress cell model. We found that compared to the GOx group, the DSRM-3716 pre-treated group reduced the hydrolysis of NAD+, inhibited the elevation of oxidative stress markers induced by GOx, decreased mitochondrial dysfunction, lowered the phosphorylation level of JNK, and attenuated the occurrence of pyroptosis in retinal and nerve cells, thereby providing protection for neurite growth. Further utilization of the JNK activator Anisomycin activated JNK, revealed that the JNK/c-Jun pathway down-regulated NMNAT2 expression. Consequently, it reduced cellular NAD+ synthesis, exacerbated mitochondrial dysfunction and cell pyroptosis, and reversed the protective effect of DSRM-3716 on cells. In summary, the inhibition of SARM1 NADase activity substantially mitigates oxidative damage to retinal cells and mitochondrial damage. Additionally, JNK simultaneously serves as both an upstream and downstream regulator in the SARM1-NAD+ axis, regulating retinal cell pyroptosis and neurite injury. Thus, this study provides new insights into the pathological processes of retinal cell oxidative stress and identifies potential therapeutic targets for retinal neurodegenerative diseases.

Transcriptome analysis of salivary glands of rabies-virus-infected mice.

Rabies is a fatal zoonotic disease that poses a threat to public health. Rabies virus (RABV) is excreted in the saliva of infected animals, and is primarily transmitted by bite. The role of the salivary glands in virus propagation is significant, but has been less studied in the pathogenic mechanisms of RABV. To identify functionally important genes in the salivary glands, we used RNA sequencing (RNA-seq) to establish and analyze mRNA expression profiles in parotid tissue infected with two RABV strains, CVS-11 and PB4. The biological functions of differentially expressed genes (DEGs) were determined by Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, which revealed 3,764 DEGs (678 up-regulated and 3,086 down-regulated) in the CVS-11 infected group and 4,557 DEGs (874 up-regulated and 3,683 down-regulated) in the PB4 infected group. Various biological processes are involved, including the salivary secretion pathway and the phosphatidylinositol 3-kinase-Akt (PI3K-Akt) signaling pathway. This study provides the first mapping of the transcriptome changes in response to RABV infection in parotid tissue, offering new insights into the study of RABV-affected salivary gland function and RABV pathogenic mechanisms in parotid tissue. The salivary gland-enriched transcripts may be potential targets of interest for rabies disease control.

The transmembrane and cytosolic domains of equine herpesvirus type 1 glycoprotein D determine Golgi retention by regulating vesicle formation.

Accumulating evidence underscores the pivotal role of envelope proteins in viral secondary envelopment. However, the intricate molecular mechanisms governing this phenomenon remain elusive. To shed light on these mechanisms, we investigated a Golgi-retained gD of EHV-1 (gDEHV-1), distinguishing it from its counterparts in Herpes Simplex Virus-1 (HSV-1) and Pseudorabies Virus (PRV). To unravel the specific sequences responsible for the Golgi retention phenotype, we employed a gene truncation and replacement strategy. The results suggested that Golgi retention signals in gDEHV-1 exhibiting a multi-domain character. The extracellular domain of gDEHV-1 was identified as an endoplasmic reticulum (ER)-resident domain, the transmembrane domain and cytoplasmic tail (TM-CT) of gDEHV-1 were integral in facilitating the protein's residence within the Golgi complex. Deletion or replacement of either of these dual domains consistently resulted in the mutant gDEHV-1 being retained in an ER-like structure. Moreover, (TM-CT)EHV-1 demonstrated a preference for binding to endomembranes, inducing the generation of a substantial number of vesicles, potentially originate from the Golgi complex or the ER-Golgi intermediate compartment. In conclusion, our findings provide insights into the intricate molecular mechanisms governing the Golgi retention of gDEHV-1, facilitating the comprehension of the processes underlying viral secondary envelopment.

Qingjie decoction attenuated E.coli-induced diarrhea by regulating energy metabolism and alleviating inflammation based on network analysis and metabolomics.

ETHNOPHARMACOLOGICAL RELEVANCE: Diarrhea is a frequently encountered gastrointestinal complication in clinical practice, and E. coli is one of the main causative agents. Although Qingjie decoction (QJD) has been shown to be highly effective in treating diarrhea by eliminating heat-toxin, the underlying molecular mechanisms and pathways of QJD remain unclear. AIM OF REVIEW: The aim of this research was to explore the effects and fundamental mechanism of QJD on diarrhea induced by E.coli in rats. MATERIALS AND METHODS: Initially, we used UHPLC-MS/MS analysis to identify the chemical composition of QJD. Then, we constructed a visualization network using network pharmacology. Next, we utilized metabolomics to identify differentially expressed metabolites of QJD that are effective in treating diarrhea. RESULTS: The chemical composition of QJD was analyzed using UHPLC-MS/MS, which identified a total of 292 components. Using a network pharmacology approach, 127 bioactive compounds of QJD were screened, targeting 171 potential diarrhea treatment targets. TNF-α, IL-6, IL-1ß, and CAT were identified as important targets through visualizing the PPI network. Enrichment analysis demonstrated significant enrichment in the TNF signaling pathway, IL-17 signaling pathway, and PI3K-Akt signaling pathway. QJD showed beneficial effects, such as increased body weight, decreased fecal water content, and reduced inflammatory cell infiltration in the duodenum and colon, as well as maintaining the structure of the duodenum and colon. Metabolomic analysis revealed 32 differentially expressed metabolites in the control, model and QJD-H groups, including glucose, valine, and cysteine. Functional analysis indicated that differential metabolites were related to energy metabolism, including glucose metabolism, TCA cycle, and amino acid metabolism. CONCLUSION: QJD significantly increased body weight, decreased water content in feces, relieved inflammatory cell infiltration, maintained the structure of duodenum and colon. Combining network analysis and metabolomics, QJD exerted therapeutic effects by inhibiting inflammation and oxidative stress, regulating glucose metabolism, tricarboxylic acid metabolism, and amino acid metabolism.

Association between Age at Menarche and Hyperhomocysteinemia among Women in Hunan, China: A Cross-Sectional Study.

Background: We aim to examine the relationship between age at menarche and hyperhomocysteinemia in women in Hunan Province. Methods: Participants were required to complete a questionnaire that included age at menarche, lifestyle habits, other baseline information, and blood biochemical parameters in a cross-sectional study. The association between hyperhomocysteinemia and age at menarche was examined by Multivariable adjusted logistic regression. Results: A cohort of 2008 women with a mean age of 60.11 years (aged from 18.0 to 88.0 years) was included in this study. After adjustment for confounding factors such as age, the results showed that the risk of hyperhomocysteinemia among women whose age at menarche were over 16 years was 2.543 (1.849, 3.469) times higher than the risk among women whose age at atmenarche were less than 14 years, and 2.656 (1.882, 3.748) times more likely to have hypertension than women with menarche at 14 years. Besides, the odds ratios of diabetes, hyperlipidemia, and obesity were elevated in women older than 16 years of age at menarche (OR = 1.924, p < 0.001; OR = 1.491, p = 0.014; OR = 1.670, p = 0.022). Conclusions: Our findings suggest that late menarche tends to be associated with a high risk of hyperhomocysteinemia and its associated set of diseases such as hypertension, diabetes, hyperlipidemia, and obesity in women in Hunan, China. This association tends to differ across birth cohorts. Therefore, adequate attention of menarcheal age may be able to predict diseases in elderly females.