Low Selenium and Low Protein Exacerbate Myocardial Damage in Keshan Disease by Affecting the PINK1/Parkin-mediated Mitochondrial Autophagy Pathway.

OBJECTIVE: Keshan disease (KD) is a myocardial mitochondrial disease closely related to insufficient selenium (Se) and protein intake. PTEN induced putative kinase 1 (PINK1)/Parkin mediated mitochondrial autophagy regulates various physiological and pathological processes in the body. This study aimed to elucidate the relationship between PINK1/Parkin-regulated mitochondrial autophagy and KD-related myocardial injury. METHODS: A low Se and low protein animal model was established. One hundred Wistar rats were randomly divided into 5 groups (control group, low Se group, low protein group, low Se + low protein group, and corn from KD area group). The JC-1 method was used to detect the mitochondrial membrane potential (MMP). ELISA was used to detect serum creatine kinase MB (CK-MB), cardiac troponin I (cTnI), and mitochondrial-glutamicoxalacetic transaminase (M-GOT) levels. RT-PCR and Western blot analysis were used to detect the expression of PINK1, Parkin, sequestome 1 (P62), and microtubule-associated proteins1A/1B light chain 3B (MAP1LC3B). RESULTS: The MMP was significantly decreased and the activity of CK-MB, cTnI, and M-GOT significantly increased in each experimental group (low Se group, low protein group, low Se + low protein group and corn from KD area group) compared with the control group (P<0.05 for all). The mRNA and protein expression levels of PINK1, Parkin and MAP1LC3B were profoundly increased, and those of P62 markedly decreased in the experimental groups compared with the control group (P<0.05 for all). CONCLUSION: Low Se and low protein levels exacerbate myocardial damage in KD by affecting the PINK1/Parkin-mediated mitochondrial autophagy pathway.

Traditional Chinese Medicine formula Dai-Zong-Fang alleviating hepatic steatosis in db/db mice via gut microbiota modulation.

Introduction: Hepatic steatosis is a hepatic pathological change closely associated with metabolic disorders, commonly observed in various metabolic diseases such as metabolic syndrome (MetS), with a high global prevalence. Dai-Zong-Fang (DZF), a traditional Chinese herbal formula, is widely used in clinical treatment for MetS, exhibiting multifaceted effects in reducing obesity and regulating blood glucose and lipids. This study aims to explore the mechanism by which DZF modulates the gut microbiota and reduces hepatic steatosis based on the gut-liver axis. Methods: This study utilized db/db mice as a disease model for drug intervention. Body weight and fasting blood glucose were monitored. Serum lipid and transaminase levels were measured. Insulin tolerance test was conducted to assess insulin sensitivity. Hematoxylin and eosin (HE) staining was employed to observe morphological changes in the liver and intestine. The degree of hepatic steatosis was evaluated through Oil Red O staining and hepatic lipid determination. Changes in gut microbiota were assessed using 16S rRNA gene sequencing. Serum lipopolysaccharide (LPS) levels were measured by ELISA. The expression levels of intestinal tight junction proteins, intestinal lipid absorption-related proteins, and key proteins in hepatic lipid metabolism were examined through Western blot and RT-qPCR. Results: After DZF intervention, there was a decrease in body weight, alleviation of glucose and lipid metabolism disorders, reduction in serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels, and mitigation of insulin resistance in mice. DZF significantly modulated the diversity of the gut microbiota, with a notable increase in the abundance of the Bacteroidetes phylum. PICRUSt indicated that DZF influenced various functions in gut microbiota, including carbohydrate and amino acid metabolism. Following DZF intervention, serum LPS levels decreased, intestinal pathological damage was reduced, and the expression of intestinal tight junction protein occludin was increased, while the expression of intestinal lipid absorption-related proteins cluster of differentiation 36 (CD36) and apolipoprotein B48 (ApoB48) were decreased. In the liver, DZF intervention resulted in a reduction in hepatic steatosis and lipid droplets, accompanied by a decrease fatty acid synthase (FASN) and stearoyl-CoA desaturase 1 (SCD1) and fatty acid transport protein 2 (FATP2). Conversely, there was an increase in the expression of the fatty acid oxidation-related enzyme carnitine palmitoyltransferase-1𝛂 (CPT-1𝛂). Conclusion: DZF can regulate the structure and function of the intestinal microbiota in db/db mice. This ameliorates intestinal barrier damage and the detrimental effects of endotoxemia on hepatic metabolism. DZF not only inhibits intestinal lipid absorption but also improves hepatic lipid metabolism from various aspects, including de novo lipogenesis, fatty acid uptake, and fatty acid oxidation. This suggests that DZF may act on the liver and intestine as target organs, exerting its effects by improving the intestinal microbiota and related barrier and lipid absorption functions, ultimately ameliorating hepatic steatosis and enhancing overall glucose and lipid metabolism.

Discovery of bioactive-chemical Q-markers of Acanthopanax sessiliflorus leaves: An integrated strategy of plant metabolomics, fingerprint and spectrum-efficacy relationship research.

An integrated bioactive-chemical quality markers (Q-markers) discovery strategy, which was based on the LC-MS plant metabolomics, HPLC fingerprint as well as the chemical spectrum-efficacy relationships, was designed to develop a methodology for accurate and comprehensive evaluation of the quality of Acanthopanax sessiliflorus leaves (ASL). Firstly, a high resolution and sensitivity UHPLC-Q-Orbitrap MS method was used for plant metabolomics analysis to obtain component characterization and screen potential chemical markers that differentiate between different harvesting periods. A total of 53 chemical components were identified, and 8 potential chemical markers were discovered, such as sucrose, maltol and phenylalanine. Secondly, a selective HPLC fingerprint analysis of ASL and its pancreatic lipase activity assay method was successfully investigated in vitro. In the study of chemical spectrum-efficacy relationships, neochlorogenic acid, chlorogenic acid, caffeic acid and hyperoside were screened and showed the inhibited pancreatic lipase activity with IC50 values, 0.16 ± 0.01, 0.13 ± 0.01, 0.31 ± 0.01, and 0.44 ± 0.02 mg/mL, respectively, which indicated the above four constituents were selected as the bioactive-chemical Q-markers of ASL. Finally, an accurate and reliable quantitative HPLC assay was developed and validated for simultaneous determination of four bioactive-chemical Q-markers in ASL, and their content levels in ASL varied widely in different harvesting periods. The systematic and efficient screening strategy for bioactive-chemical Q-markers in this study, based on " LC-MS plant metabolomics, HPLC fingerprint, and spectrum-efficacy relationships," could have effectively improved the quality assessment level of ASL.

Brief mindfulness meditation intervention improves attentional control of athletes in virtual reality shooting competition: Evidence from fNIRS and eye tracking.

Attentional control is a crucial cognitive ability for sports performance. The current research aimed to investigate whether a brief (20-min) pre-competition mindfulness meditation (MM) intervention enhances athletes' attentional control during competitions and alters the activity of brain regions related to attentional control. We created a virtual reality shooting competition to compare the eye-gaze indicators and functional near-infrared spectroscopy (fNIRS) parameters of 78 university athletes after 20 min of MM or 20 min of mind wandering (MW). Participants' average fixation durations (AFDs) on task-relevant information (targets) were significantly longer in the MM group. In contrast, both average fixation counts (AFCs) and AFDs on task-irrelevant information (the ranking screen) were significantly lower in the MM group than in the MW group. Additionally, the MM group exhibited significantly stronger activation of the left and right dorsolateral prefrontal cortex (dlPFC) as well as higher levels of oxygenated haemoglobin [HbO] and greater functional connectivity (FC) of the right dlPFC, which was considered evidence of recruitment for attentional control. Moreover, the MM group achieved significantly better shooting performance than the MW group. Overall, the findings suggest that one session 20-min MM practice pre-competition facilitates focus during competition and improves athletic performance. We recommend the application of brief mindfulness practice in sports, especially in closed-skill sports that require high attention participation (e.g., shooting, archery, darts, golf, gymnastics, skating etc.).

Effects of species mixtures on soil water storage in the semiarid hilly gully region.

Mixed-species plantations are promoted to restore degraded ecosystems and improve soil quality worldwide. However, differences of soil water conditions between pure and mixed plantations are still controversial and how species mixtures affect soil water storage (SWS) was not well quantified. In this study, vegetation characteristics, soil properties and SWS were continuously monitored and quantified in three pure plantations (Armeniaca sibirica (AS), Robinia pseudoacacia (RP) and Hippophae rhamnoides (HR)) and their corresponding mixed plantations (Pinus tabuliformis-Armeniaca sibirica (PT-AS), Robinia pseudoacacia-Pinus tabuliformis-Armeniaca sibirica (RP-PT-AS), Platycladus orientalis-Hippophae rhamnoides plantation (PO-HR), Populus simonii-Hippophae rhamnoides (PS-HR)). The results found that SWS of 0-500 cm in RP (333.60 ± 75.91 mm) and AS (479.52 ± 37.50 mm) pure plantations were higher than those in their corresponding mixed plantations (p > 0.05). SWS in the HR pure plantation (375.81 ± 81.64 mm) was lower than that in its mixed plantation (p > 0.05). It is suggested that the effect of species mixing on SWS was species specific. Additionally, soil properties exerted more contributions (38.05-67.24 %) to SWS than vegetation characteristics (26.80-35.36 %) and slope topography (5.96-29.91 %) at different soil depths and the whole 0-500 cm soil profile. Furthermore, by excluding the effects of soil properties and topographic factors, plant density and height were particularly important to SWS (with standard coefficients 0.787 and 0.690 respectively). The results implied that not all the mixed plantations exhibits the better soil water conditions than the compared pure plantations, which was tightly related to species selected for mixing. Our study provides scientific support for revegetation technique improvement (structural adjustment and species optimization) in this region.

Integrated serum pharmacochemistry, network pharmacology and pharmacokinetics to explore bioactive components of Gushudan in the treatment of osteoporosis.

Gushudan (GSD), a compound prescription on the basis of traditional Chinese medicine (TCM) theory and clinical practice, has been used in the treatment of osteoporosis (OP) for many years. Although studies have shown that GSD can treat OP, there is a lack of systematic screening method to explore the bioactive components, which are still unclear. Therefore, this study was aimed to establish an integrated method to screen and determine bioactive ingredients of GSD in the treatment of OP by serum pharmacochemistry, network pharmacology and pharmacokinetics. Firstly, 112 components of the GSD extract and 90 serum migrating constituents were identified by the ultra-high performance liquid chromatography-hybrid quadrupole-Orbitrap high-resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS), most of which were derived from flavonoids, tanshinones, coumarins and organic acids. Secondly, based on the network pharmacological analysis of the serum migrating constituents, 37 core targets and 20 main pathways related to both GSD and OP were obtained. More importantly, 7 bioactive ingredients were further screened as the PK markers by the network topology parameters including icariin, icariside II, isopimpinellin, bergapten, imperatorin, osthole and tanshinone IIA. Finally, a sensitive and accurate quantitative method based on ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) was established and validated for simultaneous determination of the 7 bioactive ingredients in the rat plasma after oral administration of GSD extract, which was then applied to pharmacokinetic study. Besides, the overall pharmacokinetic characteristics were further calculated: Cmax was 180.52 ± 31.18 ng/mL, Tmax was 0.46 ± 0.20 h, t1/2 was 4.09 ± 0.39 h, AUC0-∞ was 567.24 ± 65.29 ng·h/mL, which displayed quick absorption and medium elimination in rats after oral administration of GSD extract. This study provided a new and holistic insight for exploring bioactive constituents and main targets to decode the therapeutic material basis of GSD against OP.

The Chinese herbal medicine Dai-Zong-Fang promotes browning of white adipocytes in vivo and in vitro by activating PKA pathway to ameliorate obesity.

Introduction: The global prevalence of obesity is rising rapidly. Conversion of white adipose tissue (WAT) into beige adipose tissue with heat-consuming characteristics, i.e., WAT browning, effectively inhibits obesity. Dai-Zong-Fang (DZF), a traditional Chinese medicine formula, has long been used to treat metabolic syndrome and obesity. This study aimed to explore the pharmacological mechanism of DZF against obesity. Methods: In vivo, C57BL/6J mice were fed high-fat diets to establish the diet-induced obese (DIO) model. DZF (0.40 g/kg and 0.20 g/kg) and metformin (0.15 g/kg, positive control drug) were used as intervention drugs for six weeks, respectively. The effects of DZF on body size, blood glucose and lipid level, structure and morphology of adipocytes and browning of inguinal WAT (iWAT) in DIO mice were observed. In vitro, mature 3T3-L1 adipocytes were used as the model. Concentrations of DZF (0.8 mg/mL and 0.4 mg/mL) were selected according to the Cell Counting Kit-8 (CCK8). After 2d intervention, lipid droplet morphology was observed by BODIPY493/503 staining, and mitochondria number was observed by mito-tracker Green staining. H-89 dihydrochloride, a PKA inhibitor, was used to observe the change in browning markers' expression. The expression levels of browning markers UCP1 and PGC-1α and key molecules of PKA pathway were detected in vivo and in vitro. Results: In vivo, compared with vehicle control group, 0.40 g/kg DZF significantly reduced obesity in DIO mice from body weight, abdomen circumference, Lee's index, and WAT/body weight (p < 0.01 or p < 0.001). 0.40 g/kg DZF also significantly reduced fasting blood glucose (FBG), serum triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) (p < 0.01 or p < 0.001). The iWAT's morphology and mitochondria were browning after DZF intervention. In HE-staining, the lipid droplets became smaller, and the number of mitochondria increased. The mitochondrial structure was remodeled under the electron microscope. The expression of UCP1, PGC-1α and PKA was elevated in iWAT detected by RT-qPCR (p < 0.05 or p < 0.001). In vitro, compared with the control group, 0.8 mg/mL DZF intervention significantly increased the number of mitochondria and expression of UCP1, PGC-1α, PKA, and pCREB (p < 0.05 or p < 0.01). In contrast, UCP1 and PGC-1α expression were significantly reversed after adding PKA inhibitor H-89 dihydrochloride. Conclusion: DZF can promote UCP1 expression by activating the PKA pathway, thereby promoting browning of WAT, attenuating obesity, and reducing obesity-related glucose and lipid metabolism abnormalities, indicating that DZF has the potential to be selected as an anti-obesity drug to benefit obese patients.

Phillygenin from Forsythia suspensa leaves exhibits analgesic potential and anti-inflammatory activity in carrageenan-induced paw edema in mice.

Forsythia suspensa (Thunb.) Vahl (Oleaceae) leaves are valuable sources of phillygenin. This study aimed to isolate phillygenin from F. suspensa leaves and examine its analgesic and anti-inflammatory effects. Phillygenin was successfully extracted and isolated from F. suspensa leaves after fermentation. Phillygenin significantly reduced the number of writhing induced by acetic acid, prolonged the latency period in the hot plate test, and inhibited the xylene-induced ear edema and carrageenan-induced paw edema in mice. IL-6, TNF-α, IL-1ß, NO, and PGE2 levels in the carrageenan-induced paw edema were notably reduced after pretreatment with phillygenin. Phillygenin significantly decreased the iNOS and COX-2 protein expressions and the IκB-α and NF-κB p65 phosphorylation. This study demonstrated that phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders. The study contributes to the comprehensive development and utilization of F. suspensa leaves for economic and health care. PRACTICAL APPLICATIONS: Phillygenin is one of the major active ingredients in Forsythia suspensa. But the content of phillygenin in F. suspensa is very low which limits its application. Phillygenin has potential pharmacological activity and anti-inflammatory properties. However, the potential effects of phillygenin on analgesic activity have not been clarified. Furthermore, the data on its anti-inflammatory activity in vivo are relatively limited. This study evaluated the analgesic activity for the first time and the acute anti-inflammatory effect of phillygenin from F. suspensa leaves by fermentation, which indicated phillygenin is a potential therapeutic candidate for managing pain and inflammation-mediated disorders.

The Flow-Clutch Scale: Translation and validation study of the Chinese version.

PURPOSE: The integrated model of flow and clutch provides a multistate perspective to the optimal experiences during physical exercises. Based on this model, the Flow-Clutch Scale (FCS) was developed. The current study is the first step to test the psychometric properties of a Chinese version of the FCS (FCS-C). METHOD: A confirmatory factor analysis (CFA) with Maximum Likelihood estimate was performed in Chinese athletes (N = 426) to explore the structural validity of the FCS-C . The Pearson correlations between the subscales of the FCS-C and "non-reactivity to inner experiences", "cognitive flexibility", and "self-consciousness" were explored to examine the concurrent validity. Cronbach's alpha coefficients were used to assess the internal consistency of the total scale and subscales. Moreover, the test-retest reliability was examined in a subsample (N = 53) using a two-week interval. RESULTS: The results of CFA suggested that the three-factor model showed an acceptable model fit (χ2 = 459.40, df = 120, CFI = 0.95, GFI = 0.90, SRMR = 0.03, RMSEA = 0.082 [90% CI = 0.074-0.09]). Concerning the correlations between the factor "characteristics of flow" and "self-consciousness", the concurrent validity was not satisfactory. Moreover, the test-retest coefficients ranged from 0.75 to 0.78 (p < .01) and Cronbach's alpha ranged from 0.87 to 0.96. CONCLUSION: Results indicated that the three-factor model of FCS-C is acceptable, whereas its validity is not satisfactory to appropriately examine flow and/or clutch states in Chinese athletes. In summary, the current translation and validation study of the FCS-C allows for future research on optimal exercise experiences in Chinese-speaking cohorts including a further cultural adaptation of the questionnaire.

Modulatory action of withaferin-A on oxidative damage through regulation of inflammatory mediators and apoptosis via PI3K/AKT signaling pathway in high cholesterol-induced atherosclerosis in experimental rats.

Statins are widely used lipid-lowering drugs that cause many side effects. Withaferin-A (WA), popularly known as Ashwagandha, an ancient Indian medicinal herb, is extracted from Withania somnifera. Anti-atherosclerotic effect of WA has been reported. However, the mechanism remains unknown. Hence, we planned this study to investigate the WA mechanism in anti-atherosclerosis in a rat model. High cholesterol diet (HCD) was fed to induce atherosclerosis in Sprague-Dawley male rats. Five groups (N = 6 rats/group) were fed with normal diet, HCD, WA (10 mg/kg bw)+HCD, lovastatin (LS: 10 mg/kg bw)+HCD, WA (10 mg/kg bw) respectively for 90 days. Statistical analysis was done by GraphPad Prism (version 8.0.1) using one-way analysis of variance (ANOVA) followed by post hoc Duncan's test with a significance level (p < 0.05). The groups were compared for lipid profiles, oxidative stress, lipid peroxidation, inflammatory mediators, apoptotic markers, and histopathological changes in the liver and aorta. Treatment with HCD increased lipid profiles, inflammatory mediators, cytokines, and lipid peroxidation. WA as well as LS treatments significantly decreased these parameters restored the antioxidant status, and reduced lipid peroxidation (p < 0.05). Histopathological studies revealed that WA and LS reduced the hepatic fat and aortic plaque. WA reduced apoptosis via augmentation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway; increased B-cell lymphoma 2 and inhibited Bcl-2 associated X-protein proapoptotic proteins; TNF receptor superfamily member 6, Bim, caspase-3, and -9; demonstrated significant hypolipidemic and anti-inflammatory properties against HCD induced atherosclerosis in rats through regulation of inflammatory mediators and apoptosis via the PI3K/AKT signaling pathway.

Dietary phillygenin supplementation ameliorates aflatoxin B1-induced oxidative stress, inflammation, and apoptosis in chicken liver.

Aflatoxin B1 (AFB1), a mycotoxin contaminating food and feed, can trigger liver immune toxicity and threaten the poultry industry. Phillygenin (PHI) is a natural lignan derived primarily from Forsythia suspensa with hepatoprotective pharmacological and medicinal properties. This research aimed to investigate the preventive effects of PHI on the toxicity of AFB1 in the liver of chickens. Chickens were administered with AFB1 (2.8 mg/kg) and/or treated with PHI (24 mg/kg) for 33 days. The histopathological changes, serum biochemical indices, oxidative damage, inflammatory mediators, apoptosis, and activation of the NF-κB and Nrf2 signaling pathways were measured. Results revealed that dietary PHI ameliorated liver function indicators, reduced the malondialdehyde and inflammatory mediator production and the apoptotic cell number, and increased the antioxidant enzyme contents and Bcl-2 level. The quantitative realtime PCR and Western blot results revealed that PHI reduced p53, cytochrome c, Bax, caspase-9, and caspase-3 levels, normalized the NF-κB p65 phosphorylation, and upregulated the Nrf2 and its downstream genes expression in chicken liver. These results indicated that PHI has beneficial effects on AFB1-induced liver damage, oxidative damage, inflammatory response, apoptosis, and immunotoxicity by inhibiting NF-κB and activating the Nrf2 signaling pathway in chickens. This study provides new insight into the therapeutic uses of PHI.

Astragaloside IV promotes the angiogenic capacity of adipose-derived mesenchymal stem cells in a hindlimb ischemia model by FAK phosphorylation via CXCR2.

BACKGROUND: Therapeutic angiogenesis by transplantation of autologous/allogeneic adipose stem cells (ADSCs) is a potential method for the treatment of critical limb ischemia (CLI). However, the therapeutic efficiency is limited by poor viability, adhesion, migration and differentiation after cell transplantation into the target area. Astragaloside IV (AS-IV), one of the main active components of Astragalus, has been widely used in the treatment of ischemic diseases and can promote cell proliferation and angiogenesis. However, there is no report on the effect of AS-IV on ADSCs and its effect on hindlimb ischemia through cell transplantation. PURPOSE: The purpose of this study was to elucidate that AS-IV pretreatment enhances the therapeutic effect of ADSC on critical limb ischemia, and to characterize the underlying molecular mechanisms. METHODS: ADSCs were obtained and pretreated with the different concentration of AS-IV. In vitro, we analyzed the influence of AS-IV on ADSC proliferation, migration, angiogenesis and recruitment of human umbilical vein endothelial cells (HUVECs) and analyzed the relevant molecular mechanism. In vivo, we injected drug-pretreated ADSCs into a Matrigel or hindlimb ischemia model and evaluated the therapeutic effect by the laser Doppler perfusion index, immunofluorescence, and histopathology. RESULTS: In vitro experiments showed that AS-IV improved ADSC migration, angiogenesis and endothelial recruitment. The molecular mechanism may be related to the upregulation of CXC receptor 2 (CXCR2) to promote the phosphorylation of focal adhesion kinase (FAK). In vivo, Matrigel plug assay showed that ADSCs pretreated with AS-IV have stronger angiogenic potential. The laser Doppler perfusion index of the hindlimbs of mice in the ADSC/AS-IV group was significantly higher than the laser Doppler perfusion index of the hindlimbs of mice of the ADSC group and the control group, and the microvessel density was significantly increased. CONCLUSION: Our results demonstrate that AS-IV pretreatment of ADSC improves their therapeutic efficacy in ameliorating severe limb exclusion symptomology through CXCR2 induced FAK phosphorylation, which will bring new insights into the treatment of severe limb ischemia.

Trans-lamina terminalis suprategmental approach for ventral midbrain lesions: Technical note.

Surgical resection of lesions located in the ventral midbrain is challenging. Few approaches and safe entry zones (SEZs) have been proposed and used to remove this type of lesion, and each has its limitations. Using two illustrating cases, the authors describe a trans-lamina terminalis suprategmental approach for removing ventral midbrain lesions. This approach provides a straight surgical trajectory with sparse neurovascular structures and can be performed with a standard pterional or subfrontal craniotomy. It may be the ideal approach for ventromedial midbrain lesions extending towards the third ventricle.

Feasibility of Bone Marrow Mesenchymal Stem Cell-Mediated Synthetic Radiosensitive Promoter-Combined Sodium Iodide Symporter for Radiogenetic Ovarian Cancer Therapy.

Ovarian cancer is the most lethal gynecological cancer, most patients relapse within 12-24 months, and eventually die, especially platinum-resistant patients. Gene therapy has been one of the most potential methods for tumor treatment. Bone marrow mesenchymal stem cells (BMSCs) have been used for systemic delivery of therapeutic genes to solid tumors. Sodium iodide symporter (NIS) is an intrinsic membrane glycoprotein and can concentrate 131I, which is important for radionuclide therapy and nuclear medicine imaging in recent years. However, the rapid iodine efflux has become a bottleneck for NIS-mediated radionuclide gene therapy. Our previous studies found that the early growth response-1 (Egr1) promoter containing CC(A/T)6GG (CArG) elements had an 131I radiation-positive feedback effect on the NIS gene. Other research showed the synthesized Egr1 promoter containing four CArG elements, E4, was nearly three times as sensitive as the Egr1 promoter. In our study, BMSC-E4-NIS was engineered to express NIS under the control of E4 promoter using lentivirial vectors. After BMSC-E4-NIS implantation, no tumors were seen in BALB/c nude mice and BMSC-E4-NIS did not promote the growth of SKOV3 tumor. BMSCs migrated toward ovarian cancer samples in chemotaxis assays and to ovarian tumors in mice. Using micro-single-photon emission computed tomography/computed tomography (SPECT/CT) imaging, we found that E4 promoter produced a notable increase in 125I uptake after 131I irradiation, the radionuclide uptake is almost three and six times more than Egr1 and cytomegalovirus (CMV) promoters. These studies confirmed the feasibility of using BMSCs as carriers for lentivirus-mediated E4-NIS gene therapy for ovarian cancer. Further research on BMSC-E4-NIS gene therapy for ovarian cancer in vivo will also be carried on, and if successful, this might provide a new adjuvant therapeutical option for platinum-resistant ovarian cancer patients and provide a new method for dynamic evaluation of curative effect.

Antidepressant-Like Effects of Coumaroylspermidine Extract From Safflower Injection Residues.

In this study, a total coumaroylspermidine extract (CSE), which included four coumaroylspermidine compounds, was prepared from safflower injection (a traditional Chinese medicine) residues for the first time. The total content of the four coumaroylspermidine compounds was determined to be 64.86 ± 0.41% using high-performance liquid chromatography. We then evaluated the anti-depressant effect of CSE by using a chronic unpredictable mild stress (CUMS) model in rats. Results of sucrose preference tests, open field tests, and forced swimming tests suggest that CSE exhibits a significant anti-depressant effect. In studies to explore the mechanism, CSE was found to inhibit the increases in levels of corticosterone and decreases in levels of 5-hydroxytryptamine, dopamine, and noradrenaline induced by CUMS. Metabolic profiling showed that 10 endogenous metabolites and four metabolic pathways were altered after CSE treatment. Thus, this study not only found a spermidine extract with antidepressant effect from safflower injection residue for the first time but also provided a way for the efficient utilize of safflower injection residue.

Design, Synthesis, Molecular Docking, and Biological Evaluation of New Emodin Anthraquinone Derivatives as Potential Antitumor Substances.

The emodin anthraquinone derivatives are generally used in traditional Chinese medicine due to their various pharmacological activities. In the present study, a series of emodin anthraquinone derivatives have been designed and synthesized, among which 1,3-dihydroxy-6,8-dimethoxyanthracene-9,10-dione is a natural compound that has been synthesized for the very first time, and 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione is a compound that has never been reported earlier. Interestingly, while total seven of these compounds showed neuraminidase inhibitory activity in influenza virus with inhibition rate more than 50 %, specific four compounds exhibited significant inhibition of tumor cell proliferation. The further results demonstrate that 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione showed the best anticancer activity among all the synthesized compounds by inducing highest apoptosis rate to HCT116 cancer cells and arresting their G0/G1 cell cycle phase, through elevation of intracellular level of reactive oxygen species (ROS). Moreover, the binding of 1,3-dimethoxy-5,8-dimethylanthracene-9,10-dione with BSA protein has thoroughly been investigated. Altogether, this study suggests the neuraminidase inhibitory activity and antitumor potential of the new emodin anthraquinone derivatives.

Disrupted potassium ion homeostasis in ciliary muscle in negative lens-induced myopia in Guinea pigs.

Myopia is a main cause of preventable or treatable visual impairment, it has become a major public health issue due to its increasingly high prevalence worldwide. Currently, it is confirmed that the development of myopia is associated with the disorders of accommodation. As a dominant factor for accommodation, ciliary muscle contraction/relaxation can regulate the physiological state of the lens and play a crucial role in the development of myopia. To investigate the relationship between myopia and ciliary muscle, the guinea pigs were randomly divided into a normal control (NC) group and a negative lens-induced myopia (LIM) group, and the animals in each group were further randomly assigned into 2-week (n = 18) and 4-week (n = 21) subgroups in accordance with the duration of myopic induction of 2 and 4 weeks, respectively. In the present study, right eyes of the animals in LIM group were covered with -6.0 D lenses to induce myopia. Next, we performed the haematoxylin and eosin (H&E) staining to observe the pathological change of ciliary muscle, determined the contents of adenosine triphosphate (ATP) and lactate acid (LA), and measured the Na+/K+-ATPase expression and activity in ciliary muscles in both NC and LIM groups. Moreover, we also analyzed the potassium ion (K+) flux in ciliary muscles from 4-week NC and LIM guinea pigs. As a result, we found that the arrangements of ciliary muscles in LIM guinea pigs were broken, dissolved or disorganized; the content of ATP decreased, whereas the content of LA increased in ciliary muscles from LIM guinea pigs. Monitoring of K+ flux in ciliary muscles from LIM guinea pigs demonstrated myopia-triggered K+ influx. Moreover, we also noted a decreased expression of Na+/K+-ATPase (Atp1a1) at both mRNA and protein levels and reduced activity in ciliary muscles from LIM guinea pigs. Overall, our results will facilitate the understanding of the mechanism associated with inhibitory Na+/K+-ATPase in lens-induced myopia and which consequently lead to the disorder of microenvironment within ciliary muscles from LIM guinea pigs, paving the way for a promising adjuvant approach in treating myopia in clinical practice.

A novel circular RNA, circ-ATAD1, contributes to gastric cancer cell progression by targeting miR-140-3p/YY1/PCIF1 signaling axis.

Circular RNAs (circRNAs) has been shown to be involved in the progression of various malignancies. Nevertheless, the mechanism of dysregulated circRNAs in gastric cancer (GC) remains to be understood. CircRNA microarray was utilized for identifying circRNA expression profiles in GC tissues. Circ-ATAD1 expression was measured by qRT-PCR. The clinical significance of circ-ATAD1 was analyzed by Fisher's exact test, Kaplan-Meier plots, and Cox regression model. The function of circ-ATAD1 was explored by using CCK-8, clone formation, flow cytometric and transwell experiments. RNA sequencing, bioinformatics, RNA pulldown, chromatin immunoprecipitation followed by sequencing, and dual-luciferase reporter assays were applied to determine the regulatory networks of circ-ATAD1 in GC cells. Circ-ATAD1 expression was increased in cancerous tissues. The prognostic value of circ-ATAD1 was identified in GC patients. For GC cells, circ-ATAD1 increased cell progression by sponging miR-140-3p to upregulate YY1. Additionally, YY1 directly bound to the promoter of PCIF1, thereby activating its transcription. Collectively, circ-ATAD1 plays an important role in GC tumorigenesis and progression and might be an important biomarker/therapeutic target for GC.

Natural deep eutectic characteristics of honey improve the bioactivity and safety of traditional medicines.

ETHNOPHARMACOLOGICAL RELEVANCE: Honey, an important additive with natural deep eutectic solvent (NADES) characteristics, has been used in traditional medicine for thousands of years. AIM OF THE STUDY: We investigated the quality-improving effects of honey on Astragali Radix (Mikvetch Root) (RA) as an example. MATERIALS AND METHODS: Decoctions of raw RA, fried RA, honey-fried RA, and a man-made- honey-fried RA were prepared and compared in cell-based bioactivity tests, chemical composition tests, as well as a bioavailability test with calycosin-7-O-ß-D-glucoside. RESULTS: The addition of honey increased the concentrations of active compounds and their oral bioavailability, provided protection against acetylation, and consequently increased their bioactivity. These changes were also observed when a pure NADES-mimicking honey was used. CONCLUSION: Our findings provide a potential explanation as to why honey has long been used as traditional medicine additives and rationalize the application of honey and honey-like substance in producing pharmaceuticals.

Resection might be a meaningful choice for hepatocellular carcinoma with portal vein thrombosis: A systematic review and meta-analysis.

BACKGROUND: According to the Barcelona Clinic Liver Cancer (BCLC) staging system, the presence of portal vein tumor thrombosis (PVTT) is considered to indicate an advanced stage of hepatocellular carcinoma (HCC) with nearly no cure. Hepatic resection and transarterial chemoembolization (TACE) have recently been recommended for treatment of HCC with PVTT. METHODS: We conducted a systematic review to compare the overall survival between patients with HCC and PVTT undergoing hepatectomy, TACE or conservative treatment including sorafenib chemotherapy. The PubMed, Web of Science, and Cochrane Library databases were searched. All relevant studies were considered. Hazard ratios with 95% confidence intervals were calculated for comparison of the cumulative overall survival. Ten retrospective studies met the inclusion criteria and were included in the review. RESULTS: Overall survival was not higher in the hepatectomy group than TACE group. But survival rate was higher in hepatectomy group than conservative group. The subgroup analysis demonstrated that hepatectomy was superior in patients without PVTT in the main trunk than in patients with main portal vein invasion. In patients without main PVTT, hepatectomy has showed more benefit than TACE. However, there has been no significant difference between the hepatectomy and TACE groups among patients with main PVTT. CONCLUSION: For patients with resectable HCC and PVTT, hepatectomy might be more effective in patients without PVTT in the main trunk than TACE or conservative treatment.