Probing the structural evolution on the surface of cardiolipin vesicles with an amphiphilic second harmonic generation and fluorescence probe.

Investigating the influence of the ambient chemical environment on molecular behaviors in liposomes is crucial for understanding and manipulating cellular vitality as well as the capabilities of lipid drug carriers in various environments. Here, we designed and synthesized a second harmonic generation (SHG) and fluorescence probe molecule called Pyr-Py+-N+ (PPN), which possesses membrane-targeting capability. We employed PPN to investigate the response of lipid vesicles composed of cardiolipin to the presence of exogenous salt. The kinetic behaviors, including the adsorption and embedding of PPN on the surface of small unilamellar vesicles (SUVs) composed of cardiolipin, were analyzed. The response of the SUVs to the addition of NaCl was also monitored. A rapid decrease in vesicle size can be evidenced through the rapid drop in SHG emission originating from PPN located on the vesicle surface.

Temperature-Modulated Evolution of Surface Structures Induces Significant Enhancement of Two-Photon Fluorescent Emission from a Dye Molecule.

Fluorescence is an essential property of molecules and materials that plays a pivotal role across various areas such as lighting, sensing, imaging, and other applications. For instance, temperature-sensitive fluorescence emission is widely utilized for chemo-/biosensing but usually decreases the intensity upon the increase in temperature. In this study, we observed a temperature-induced enhancement of up to ∼150 times in two-photon fluorescence (TPF) emission from a dye molecule, 4-(4-diethylaminostyry)-1-methylpyridinium iodide (D289), as it interacted with binary complex vesicles composed of two commonly applied surfactants: sodium dodecyl sulfate (SDS) and cetyltrimethylammonium bromide (CTAB). By employing second harmonic generation (SHG) and TPF techniques, we clearly revealed the temperature-dependent kinetic behavior of D289 on the surface of the vesicles and utilized it to interpret the origin of the significant TPF enhancement. Additionally, we also demonstrated a similar heating-induced enhancement of the TPF emission from D289 on the membrane of phospholipid vesicles, indicating the potential application of TPF in temperature sensing in the biology systems. The embedding of D289 in the tightly packed alkane chains was identified as the key factor in enhancing the TPF emission from D289. This finding may provide valuable information for synthesizing fluorescence materials with a high optical yield.

Monitoring the response of a model protocell to dye and surfactant molecules through second harmonic generation and fluorescence imaging.

Probing the interaction between molecules and protocells is crucial for understanding the passive transport of functional molecules in and out of artificial and real cells. Second-harmonic generation (SHG) has been proven to be a powerful method for analyzing the adsorption and cross-membrane transport of molecules on lipid bilayers. In this study, we used SHG and two-photon fluorescence (TPF) imaging to study the interaction of charged dye molecules (D289) with a lipid vesicle. Unexpectedly, it was observed that the transport of D289 at a relatively high concentration is not as efficient as that at a lower dye concentration. Periodic shrinking of the model protocell and discharging of D289 out from the vesicle were revealed by combined analyses of SHG and TPF images. The response of the vesicle to a surfactant was also analyzed with D289 as a probe. This work demonstrates that the combined SHG and TPF imaging method is a unique approach that can provide detailed information on the interaction of molecules and lipids (both morphology and molecular kinetics). Determining these subtle interfacial kinetics in molecules is important for understanding the mechanism of many biophysical processes occurring on lipids.

Identifying Molecular Subtypes and 6-Gene Prognostic Signature Based on Hypoxia for Optimizing Targeted Therapies in Non-Small Cell Lung Cancer.

Background: Non-small cell lung cancer (NSCLC) accounts for a great number of all lung cancer cases. Hypoxia, one of the hallmarks in solid cancer, is closely involved in cancer cell progression and migration. This study aimed to develop a molecular subtyping system based on hypoxia-related genes and construct a prognostic model for NSCLC patients. Methods: Unsupervised consensus clustering was used to classify molecular subtypes. Mutation and immune analyses were conducted to compare differences among the molecular subtypes. Univariate Cox regression, least absolute shrinkage and selection operator (LASSO) analysis, and step Akaike information criterion (stepAIC) were performed to screen prognostic genes. Results: Two molecular subtypes (C1 and C2) were identified based on hypoxia-related genes and showed significant differences in survival, enriched pathways, tumor microenvironment (TME), and sensitivity to immunotherapy and chemotherapy. Interestingly, C1 subtype had better survival and response to targeted therapies. Oncogenic pathways, such as hypoxia, epithelial mesenchymal transition (EMT), NOTCH signaling, and p53 signaling pathways were more enriched in C2 subtype. A 6-gene prognostic model with robust ability was developed to classify NSCLC patients into high-risk and low-risk groups. Conclusion: The novel molecular subtypes could assist personalized therapies to select suitable patients. The six prognostic genes may be novel targets for further understanding mechanisms of NSCLC development associated with hypoxia and exploiting novel targeted therapies.

Role of Parameter Setting in Electroacupuncture: Current Scenario and Future Prospects.

Acupuncture is an ancient therapeutic method based on the theory of Chinese medicine (CM). Traditional acupuncture has many limitations; it is subjective and relies more on the experience of an acupuncturist, and the efficacy is sometimes irreproducible. In contrast, electroacupuncture (EA) has special characteristics in terms of objectivity and stability, thereby gaining considerable attention. Parameter setting plays a crucial role in EA practice. The current paper summarizes the current situation and limitations of parameter setting in EA practice. Objectification is the tendency and future of CM as well as EA. With the development of computerized technologies, such as wearable sensors, vast data, and artificial intelligence, CM syndromes can be successfully objectified. We propose the development of a novel self-feedback-adjust EA system, which may improve the parameter setting in EA and be beneficial to both the patients and clinicians.

Serum Metabolic Profiles of Chinese Women With Perimenopausal Obesity Explored by the Untargeted Metabolomics Approach.

By far, no study has focused on observing the metabolomic profiles in perimenopause-related obesity. This study attempted to identify the metabolic characteristics of subjects with perimenopause obesity (PO). Thirty-nine perimenopausal Chinese women, 21 with PO and 18 without obesity (PN), were recruited in this study. A conventional ultra-high-performance liquid chromatography-quadrupole time-of-flight/mass spectrometry (UHPLC-QTOF/MS) followed by principal component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) were used as untargeted metabolomics approaches to explore the serum metabolic profiles. Kyoto Encyclopedia of Genes and Genomes (KEGG) and MetaboAnalyst were used to identify the related metabolic pathways. A total of 46 differential metabolites, along with seven metabolic pathways relevant to PO were identified, which belonged to lipid, amino acids, carbohydrates, and organic acids. As for amino acids, we found a significant increase in l-arginine and d-ornithine in the positive ion (POS) mode and l-leucine, l-valine, l-tyrosine, and N-acetyl-l-tyrosine in the negative ion (NEG) mode and a significant decrease in l-proline in the POS mode of the PO group. We also found phosphatidylcholine (PC) (16:0/16:0), palmitic acid, and myristic acid, which are associated with the significant upregulation of lipid metabolism. Moreover, the serum indole lactic acid and indoleacetic acid were upregulated in the NEG mode. With respect to the metabolic pathways, the d-arginine and d-ornithine metabolisms and the arginine and proline metabolism pathways in POS mode were the most dominant PO-related pathways. The changes of metabolisms of lipid, amino acids, and indoleacetic acid provided a pathophysiological scenario for Chinese women with PO. We believe that the findings of this study are helpful for clinicians to take measures to prevent the women with PO from developing severe incurable obesity-related complications, such as cardiovascular disease and stroke.

Verification of the Efficacy and Safety of Qi-Replenishing Chinese Medicine in Treating Prediabetes: A Meta-Analysis and Literature Review.

BACKGROUND: Qi-replenishing Chinese medicines (QCMs) are used for treating prediabetes in the traditional Chinese medicine (TCM) clinical practice. The aims of this meta-analysis were to (i) verify the efficacy and safety of QCMs in treating prediabetes and (ii) investigate the clinical outcomes between the trials complying with and not complying with the principle of "syndrome differentiation." METHODS: We included only randomized controlled clinical trials (RCTs) whose Jadad scores were not less than 4. The overall clinical outcomes, including the incidence rate of diabetes, normalization of blood glucose, changes in fasting blood glucose (FBG), 2 h postprandial blood glucose, HbA1c, and occurrence of adverse events, were evaluated. Subgroup analyses were performed. RESULTS: A total of 11 RCTs that enrolled 2210 patients with prediabetes were included. We observed that overall treatment with QCMs significantly ameliorated the clinical outcomes of prediabetes without increasing incidence of adverse events. The results of subgroup analyses revealed that prescribing QCMs complying with syndrome differentiation ameliorated all the clinical indices, whereas prescribing not complying with syndrome differentiation could not achieve significant amelioration in FBG and HbA1c levels. Furthermore, the subgroup with syndrome differentiation reported more adverse events. CONCLUSIONS: The overall results suggested that QCMs are effective and safe in treating prediabetes. Results of subgroup analyses indicated that the groups with syndrome differentiation presented better efficacy but had a higher occurrence of adverse events. This study indicated the important role of the principle of syndrome differentiation in TCM and that the adverse events of QCMs cannot be ignored in TCM clinical practice.

Factor and Cluster Analysis for TCM Syndromes of Real-World Metabolic Syndrome at Different Age Stage.

BACKGROUND: Traditional Chinese medicine (TCM) has the characteristics of multitarget and overall regulation, which has certain advantages in preventing and treating of metabolic syndrome (MS). The aim of the present study was to evaluate the similarities and differences of TCM syndrome distribution in different age groups to promote the optimization of treatment strategies. METHODS: This study was based on a real-world survey conducted in 3 hospitals in China. There are 1262 collected cases of MS meeting the inclusion criteria, which were divided into the young group, middle-aged group, and elderly group. Factor analysis (FA) was conducted for syndrome element extraction, and K-means cluster analysis was processed for syndrome type classification. Frequency analysis and Chi-square test were used to compare the syndrome characteristics of each group. RESULTS: Common factors extracted were assigned to 18 syndrome elements including 11 nature syndrome elements and 7 location syndrome elements. Phlegm and dampness are the most frequent syndrome elements in general. Compared with the middle-aged group and elderly group, the young group has more obvious nature syndrome elements in heat and Qi deficiency, and location syndrome elements in the stomach. As for the middle-aged group, the frequency of location syndrome in kidney syndrome was higher than that in other groups. When it comes to the elderly group, it is shown that the symptoms of Yin deficiency and blood deficiency increase with age and the old patients may have more location syndrome elements in the lung and gallbladder. CONCLUSION: The TCM syndrome of MS is complex in that there may be the characteristics of deficiency and excess syndrome simultaneously. The main pathological factors of MS were phlegm and dampness. Besides, MS patients at different age periods may have their own syndrome distribution features. So, it is reasonable to adhere to the method of resolving phlegm and removing dampness and, at the same time, adopt the ways of clearing heat, promoting Qi, nourishing Yin, supplementing blood as well as regulating the liver, promoting the lung, transporting the spleen, nourishing the heart, and nourishing the kidney based on the syndrome feature of MS in different age stages.

Serum Metabolomic Profiles Associated With Untreated Metabolic Syndrome Patients in the Chinese Population.

Metabolomics is a promising technology for elucidating the mechanisms of metabolic syndrome (MetS). However, measurements in patients with MetS under different conditions vary. Metabolomics experiments in different populations and pathophysiological conditions are, therefore, indispensable. We performed a serum metabolomics investigation in untreated patients with MetS in the Chinese population. Untreated patients with MetS were recruited to this study. Metabolites were measured using a traditional 1 H nuclear magnetic resonance (NMR) experiment followed by principal component analysis (PCA) and orthogonal partial least squares discriminant analysis (OPLS-DA). Key metabolic pathways were identified by searching the Kyoto Encyclopedia of Genes and Genomes Pathway Database. A total of 28 patients with MetS and 30 healthy subjects were enrolled. All patients were untreated because they were unaware of or neglected to treat their MetS. By 1 H NMR, we identified 49 known substances. Following PCA and OPLS-DA, 36 metabolites were confirmed to be closely associated with MetS compared with the control group; 33 metabolites were increased, whereas 3 metabolites were reduced. Importantly, 14 metabolites that changed in the serum of these untreated patients with MetS were previously unreported. Pathway analysis revealed the top 15 metabolic pathways associated with untreated MetS, which included 3 amino acid metabolic pathways. Our data suggest that untreated patients exhibit a worse pathophysiologic manifestation, which may result in more rapid progression of MetS. Thus, we propose that health education be reinforced to improve the public's knowledge, attitude, and practice regarding MetS. The rates of "untreated" patients due to unawareness and neglect must be reduced immediately.

Triphenylamine/carbazole-modified ruthenium(ii) Schiff base compounds: synthesis, biological activity and organelle targeting.

Four triphenylamine/carbazole-modified half-sandwich ruthenium(ii) compounds [(η6-p-cymene)Ru(N/O^N)Cl]0/+ with Schiff base chelating ligands (N/O^N) are synthesized and characterized. The introduction of Schiff base units effectively increases the antitumor activity of these compounds (IC50: 1.70 ± 0.56-17.75 ± 3.10 µM), which, meanwhile, can inhibit the metastasis of tumor cells effectively. These compounds follow an energy-dependent cellular uptake mechanism, mainly accumulate in lysosomes to destroy their integrity, and then eventually promote apoptosis. In addition, these compounds can induce an increase of intracellular reactive oxygen species (ROS) levels and provide an antitumor mechanism of oxidation, which is confirmed by the decrease of mitochondrial membrane potential (MMP) and the catalytic oxidation of the coenzyme nicotinamide-adenine dinucleotide (NADH). All these indicate that these ruthenium(ii) compounds are expected to be dual-functional antitumor agents: anti-metastasis and lysosomal damage.

Problems lowering the study quality in traditional medicine, introspection from an example of meta-analysis of acupuncture.

BACKGROUND: Most randomized controlled trials (RCTs) of traditional medicine (such as traditional Chinese medicine (TCM), psychotherapy or behavioral therapy, and dietary interventions, etc.) have reported that they could not provide convincing evidence to support the efficacy because of the low quality of their studies. Here, we aimed to determine the underlying problems of the study quality using standards of evidence-based medicine (EBM) to evaluate the efficacy of traditional medicine. METHODS: We conducted an example of meta-analysis to evaluate the efficacy of acupuncture, a classical treatment of TCM, for treatment of intracerebral hemorrhage (ICH). The quality of the included studies was evaluated by using a Jadad score. RESULTS: A total of 24 Chinese RCTs that enrolled 1815 patients with ICH were included. Although the results suggested that acupuncture had good efficacy for relief of neurological deficits and improvement of the activities of daily living despite the high heterogeneity of the included studies, the low quality of the included literature reduced the worthiness of the evidence. Two systematic problems (lack of blinding and allocation concealment and high heterogeneity) and one non-systematic problem (lack of reports on adverse events and follow-up) of the TCM studies were found in this illustrational meta-analysis. We believed that other interventions of traditional medicine also suffer from these problems. CONCLUSIONS: Non-systematic problems can be improved by perfecting the experimental design, educating the researcher, and improving the reporting system. However, systematic problems are derived from the characteristics of traditional medicine that are difficult to be corrected. We propose that adoption of objective indexes might be a better solution to improve the systematic problems of traditional medicine. We summarized the problems and the underlying solutions, which may contribute to improve the study quality of systematic review in traditional medicine, strictly complying with the principles of EBM.

Dual functions of iridium(III) 2-phenylpyridine complexes: Metastasis inhibition and lysosomal damage.

Six N-phenylcarbazole/triphenylamine-appended half-sandwich iridium(III) 2-phenylpyridine complexes ([(η5-Cp*)Ir(C^N)Cl]) were prepared and characterized. Compared with cisplatin, these complexes exhibited potential antitumor activity against A549 and HeLa tumor cells, with IC50 values (half-maximum inhibitory concentration) that changed from 2.8 ± 0.8 µM to 39.5 ± 2.7 µM, and could block the migration of tumor cells. These complexes also effectively bound to protein (binding constant: ~104 M-1) and were transported through serum proteins, catalyzed the oxidation of coenzyme nicotinamide-adenine dinucleotide. Additionally, laser confocal microscopy and flow cytometry confirmed that these complexes possessed a non-energy-dependent cellular uptake mechanism, effectively accumulated in lysosomes (Pearson colocalization coefficient: ~0.74), damaged the integrity of acidic lysosomes, led to a change in the mitochondrial membrane potential, disrupted the cell cycle (G0/G1 phase), and eventually induced apoptosis. Above all, these complexes are potential antitumor agents with dual functions: metastasis inhibition and lysosomal damage.

Risk analysis of systemic levels of estrogen and adipokines as well as estrogen receptors from PBMCs in childbearing and perimenopausal women with obesity.

PURPOSE: We aimed to evaluate the clinical value of systemic levels of estrogen and adipokines as well as estrogen receptors from peripheral blood mononuclear cells (PBMCs) in childbearing and perimenopausal women with obesity. SUBJECTS AND METHODS: We observed 292 women, including 160 perimenopausal women (80 with obesity and 80 without obesity) and 132 women of childbearing age (67 with obesity and 65 without obesity). Body parameters, such as body mass index and waist circumference, were measured. Fat distribution was evaluated using a computerized tomography scanner. The levels of serum estrogen, leptin, visfatin, and adiponectin were measured using an enzyme-linked immunosorbent assay. The expression of circulating ERs was evaluated by Western blot analysis. RESULTS: Perimenopausal women and childbearing women with obesity exhibited lower levels of estrogen and adiponectin, in addition to a distribution of visceral fat with higher levels of leptin and visfatin. These findings reflect the current data of menopausal women, which confirms the reliability of this experimental system. However, the expression of ERα in peripheral blood was significantly enhanced in women with obesity of both childbearing and perimenopausal age. This result is contrary to the common understanding of adipose tissue, namely that ERα is protective. The expression of ERß in the women without obesity of both childbearing and perimenopausal age was higher than in women with obesity, which coincides with the results of a previous study on adipose tissue. CONCLUSION: Our data fundamentally contradicts the utility of circulating ERα and ERα/ERß evaluations in obesity studies. Because estrogen exerts pleiotropic effects on multiple tissues in the body through differential regulation of ERs, although the expression of ERß coincides with the results of a previous study on adipose tissue, the expression levels of ERs in blood cannot be used as a diagnostic of informative tool for obesity in women.

Ferrocene-Appended Iridium(III) Complexes: Configuration Regulation, Anticancer Application, and Mechanism Research.

A series of ferrocene-appended half-sandwiched iridium(III) phenylpyridine complexes have been designed and synthesized. These complexes show better anticancer activity than cisplatin widely used in clinic under the same conditions. Meanwhile, complexes could effectively inhibit cell migration and colony formation. Complexes could interact with protein and transport through serum protein, effectively catalyzing the oxidation of nicotinamide-adenine dinucleotid and inducing the accumulation of reactive oxygen species (ROS, 1O2), which confirmed the anticancer mechanism of oxidation. Furthermore, laser scanning confocal detection indicates that these complexes can enter cells followed by a non-energy-dependent cellular uptake mechanism, effectively accumulating in the lysosome (Pearson's colocalization coefficient: ∼0.90), leading to lysosome damage, and reducing the mitochondrial membrane potential (MMP). Taken together, ferrocene-appended iridium(III) complexes possess the prospect of becoming a new multifunctional therapeutic platform, including lysosome-targeted imaging and anticancer drugs.

Mechanisms Underlying the Prevention and Treatment of Cholelithiasis Using Traditional Chinese Medicine.

Cholelithiasis is a major public health concern that necessitates highly effective, feasible, and recurrence-preventing therapies. Currently available surgical treatments and medications cannot effectively avoid the recurrence of cholelithiasis. Hence, several Chinese herbal compounds (CHCs) are considered for the treatment of cholelithiasis, considering that they can effectively discharge gallstones and prevent the recurrence of such condition. In the present narrative review, we aim to summarize the underlying mechanisms of currently used CHCs in the treatment of cholelithiasis and to describe the current situation of traditional Chinese medicine (TCM) use for cholelithiasis. Several commonly used CHCs were used to illustrate these issues. We found that the mechanisms underlying the CHC treatments rely on the amelioration of the biliary dynamics factors, maintenance and protection of the liver function, reduction of the cholesterol and bilirubin levels, and regulation of the inflammatory reactions. CHCs as treatments based on TCM can ameliorate the overall bodily function, thereby preventing the recurrence of cholelithiasis. Appropriate application of CHCs would be beneficial for patients and clinicians, although the safety and efficacy of CHCs need further verification.

Can the Latest Computerized Technologies Revolutionize Conventional Assessment Tools and Therapies for a Neurological Disease? The Example of Parkinson's Disease.

Dramatic breakthroughs in the treatment and assessment of neurological diseases are lacking. We believe that conventional methods have several limitations. Computerized technologies, including virtual reality, augmented reality, and robot assistant systems, are advancing at a rapid pace. In this study, we used Parkinson's disease (PD) as an example to elucidate how the latest computerized technologies can improve the diagnosis and treatment of neurological diseases. Dopaminergic medication and deep brain stimulation remain the most effective interventions for treating PD. Subjective scales, such as the Unified Parkinson's Disease Rating Scale and the Hoehn and Yahr stage, are still the most widely used assessments. Wearable sensors, virtual reality, augmented reality, and robot assistant systems are increasingly being used for evaluation of patients with PD. The use of such computerized technologies can result in safe, objective, real-time behavioral assessments. Our experiences and understanding of PD have led us to believe that such technologies can provide real-time assessment, which will revolutionize the traditional assessment and treatment of PD. New technologies are desired that can revolutionize PD treatment and facilitate real-time adjustment of treatment based on motor fluctuations, such as telediagnosis systems and "smart treatment systems." The use of these technologies will substantially improve both the assessment and the treatment of neurological diseases before next-generation treatments, such as stem cell and genetic therapy, and next-generation assessments, can be clinically practiced, although the current level of artificial intelligence cannot replace the role of clinicians.

Current behavioral assessments of movement disorders in children.

Pediatric movement disorders (PMDs) are common and have recently received increasing attention. As these disorders have special clinical features, the selection of appropriate behavioral assessment tools that can clearly distinguish movement disorders from other diseases (eg, epilepsy and neuromuscular disorders) is crucial for achieving an accurate diagnosis and treatment. However, few studies have focused on behavioral assessments in children. The present report attempts to provide a critical review of the available subjective and objective assessment tests for common PMDs. We believe that the principles of objectification, multi-purpose use, and simplification are also applicable to the selection and development of satisfactory pediatric behavioral assessment tools. We expect that the development of wearable sensors, virtual reality, and augmented reality will lead to the establishment of more reliable and simple tests. In addition, more rigorous randomized controlled trials that have been specifically designed to evaluate behavioral testing in children are also expected in the future.

The antidepressant-like effects of Chaihu Shugan San: Dependent on the hippocampal BDNF-TrkB-ERK/Akt signaling activation in perimenopausal depression-like rats.

Chaihu Shugan San (CSS), a traditional Chinese medicine formula, has been used to treat depression for hundreds of years. Recently, the antidepressant-like mechanism of CSS has been increasingly evaluated and demonstrated. However, there are few studies focused on the involvement of the neurotrophic system in mediating the antidepressant-like effects of CSS. Considering the high prevalence of perimenopausal depression around the world, the goal of the present study was to determine whether brain-derived neurotrophic factor (BDNF) signaling is required for the antidepressant-like effects of CSS in perimenopausal depressive-like rats. The results indicate that CSS reverses depressive-like behaviors and attenuates the downregulation of BDNF in the hippocampus of perimenopausal rats exposed to chronic unpredictable mild stress (CUMS). We found that the TrkB antagonist K252 not only blocks the effects of CSS on behavioral improvement but also abolishes the activation of CSS in BDNF-TrkB signaling. As a result, the downstream targets of BDNF signaling, such as the ERK and Akt pathways, are significantly inhibited by K252a. Furthermore, CSS increases hippocampal neurogenesis, while K252a fully prevents this action. In conclusion, the present results demonstrate that the activation of the hippocampal BDNF-TrkB-ERK/Akt signaling pathway is required for the antidepressant-like effects of CSS on the depressive-like state during perimenopause. Additionally, this study also demonstrates that neurogenesis is required for the effects of antidepressants in aging perimenopausal animals and provides fundamental evidence for the clinical application of CSS.

Saikosaponin A attenuates perimenopausal depression-like symptoms by chronic unpredictable mild stress.

Accumulating studies have shown that a traditional Chinese decoction Chaihu-Shugan-San produced the antidepressant-like effects in rodents including in perimenopausal. Previous studies and our preliminary study indicated that saikosaponin A, one of the main constituents of Chaihu-Shugan-San, enhanced brain-derived neurotrophic factor (BDNF) expression in rats. Herein, this study aimed to evaluate the antidepressant-like effects of saikosaponin A in perimenopausal rats exposed to chronic unpredictable mild stress (CUMS). The sucrose preference test, novelty-suppressed feeding test and forced swimming test were performed after administration of saikosaponin A for 4 weeks. Serum corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH) and corticosterone levels, as well as hypothalamus CRH and hippocampal glucocorticoid receptor were measured. In addition, pro-inflammatory cytokines such as interleukin-1beta (IL-1ß), interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) in the hippocampus were detected for evaluation of the neuroinflammation. Further, BDNF levels and its receptor TrkB were also determined. Our results indicated that four-week treatment with saikosaponin A increased sucrose preference, decreased latency to feed in the novelty-suppressed feeding test and reduced the immobility time in the forced swimming test. In addition, saikosaponin A restored the dsyregulation of HPA axis and neuroinflammation in rats exposed to CUMS. Moreover, saikosaponin A promoted BDNF-TrkB signaling in the hippocampus. This study demonstrates that saikosaponin A produced the antidepressant-like effects in rats, which may be mediated by restoration of neuroendocrine, neuroinflammation and neurotrophic systems in the hippocampus during perimenopausal.

Promoter methylation of p16 and RASSF1A genes may contribute to the risk of papillary thyroid cancer: A meta-analysis.

The aim of the present meta-analysis was to investigate the correlation of promoter methylation of the p16 and Ras association domain family 1 isoform A (RASSF1A) genes with the risk of the development of papillary thyroid cancer (PTC). A number of electronic databases were searched without language restrictions as follows: Medline (1966-2013), the Cochrane Library database (Issue 12, 2013), Embase (1980-2013), CINAHL (1982-2013), Web of Science (1945-2013) and the Chinese Biomedical Database (CBM; 1982-2013). A meta-analysis was performed with the use of Stata statistical software. The odds ratios (ORs), ratio differences (RDs) and 95% confidence intervals (95% CIs) were calculated. In the present meta-analysis, eleven clinical cohort studies with a total of 734 patients with PTC were included. The results of the current meta-analysis indicated that the frequency of promoter methylation of p16 in cancer tissues was significantly higher compared with that in normal, adjacent and benign tissues (cancer tissues vs. normal tissues: OR=7.14; 95% CI, 3.30-15.47; P<0.001; cancer tissues vs. adjacent tissues: OR=11.90; 95% CI, 5.55-25.52; P<0.001; cancer tissues vs. benign tissues: OR=2.25; 95% CI, 1.67-3.03; P<0.001, respectively). The results also suggest that RASSF1A promoter methylation may be implicated in the pathogenesis of PTC (cancer tissues vs. normal tissues: RD=0.53; 95% CI, 0.42-0.64; P<0.001; cancer tissues vs. adjacent tissues: RD=0.39; 95% CI, 0.31-0.48; P<0.001; cancer tissues vs. benign tissues: RD=0.39; 95% CI, 0.31-0.47; P<0.001; respectively). Thus, the present meta-analysis indicates that aberrant promoter methylation of p16 and RASSF1A genes may play a crucial role in the pathogenesis of PTC.