The effectiveness of online group mindfulness-based cognitive therapy for outpatients with depression in China.

OBJECTIVES: With the development of online technology and the increase in real-world needs, conducting psychotherapy on online platforms has become a popular trend. The present study followed the schedule and content of Mindfulness-based Cognitive Therapy (MBCT), and only changed the treatment format (from offline to online) to investigate the effectiveness of online group MBCT for Chinese outpatients with depression. METHODS: The study used before-and-after controlled design, and included 88 depressed outpatients, of which 75 formally underwent a 10-week online group MBCT. The 24-item Hamilton Depression Scale (HAMD-24), Hamilton Anxiety Scale (HAMA), Self-Depression Rating Scale (SDS), Mindful Attention Awareness Scale (MAAS), and Self-Acceptance Questionnaire (SAQ) were administered to patients one week prior to treatment, the fifth week of treatment, and the tenth week of treatment. Repeated-measures data were processed using linear mixed-effects models. RESULTS: 75 patients (85.23 %) attended >4 sessions, 44 of whom were taking psychotropic medication during treatment. HAMD-24 and HAMA scores decreased significantly in both medicated and unmedicated patients (w10 < w1, p < 0.05). HAMD-24 and HAMA scores declined more rapidly in patients taking medication, with significant decreases in the fifth week (w5 < w1, p < 0.05). The remarkable effectiveness of treatment (HAMD-24 score reduction >50 %) was >30 %, but there were no significant changes in patients' SDS, MAAS, or SAQ scores. CONCLUSIONS: This study supports the effectiveness of online group MBCT for outpatients with depression and the adherence of depressed patients to participate in online group MBCT was high.

Lipidomics-based analysis of lipid differences between dry skin of women aged 22-28 years and 29-35 years.

BACKGROUND: The skin condition of women is different at different ages, and skin surface lipids are also different. According to the "7-7 theory" of the Huangdi Neijing, the physiological condition of women changes significantly every 7 years, and women aged 22-28 are in the "4-7" stage as mentioned in the "7-7 theory" of the Huangdi Neijing. Women's skin is in different states at different ages and produces different lipids. OBJECTIVES: To explore the key lipids that contribute to skin differences between women aged 22-28 and 29-35 years, and to explore the relationship with physiological parameters and daily routine. METHODS: Differential lipids were detected and screened between 22-28 year old (group D1) and 29-35 year old (group D2) dry-skinned women using UPLC-Q-TOF-MS and correlated between the two groups with questionnaires and physiological parameters based on basic information, lifestyle habits, work situation, and emotional stress. RESULTS: The results showed that all of the eight major classes of lipids had the highest expression in the D2 group, with the largest differences in glycerophospholipids, glycerol esters, and fatty acids. The BMI value of D2 group was higher than that of D1 group, the skin elasticity index (R2) and brightness index (L, a, ITA values) were lower than that of D1 group, and Cer (d18:0/16:0) was positively correlated with the R2, L, a, and ITA, and LMSP01080056 (N,N-dimethyl-Safingol) was positively correlated with the b-value, the LMSPGP03020013, LMSPGP03020014, LMSP03020024 were significantly negatively correlated with R2. CONCLUSIONS: Cer(d18:0/16:0) is a neurosphingol that inhibits elastase expression. N,N-dimethyl-Safingol readily undergoes oxidation to form yellow-brown solids. The macromolecular structure and excessive carbonyl structure of [LMGP0302] are susceptible to cross-linking and carbonyl stress reactions, which accelerate skin aging and reduce skin elasticity, and thus, they may be key lipids contributing to skin differences between the two age groups.

Oral CoQ10 attenuates high salt-induced hypertension by restoring neurotransmitters and cytokines in the hypothalamic paraventricular nucleus.

High salt intake leads to an increase in some proinflammatory cytokines and neurotransmitters involved in the pathogenesis of hypertension. The purpose of this work was to know if oral administration of anti-oxidant and free-radical scavenger CoQ10 may attenuate high salt-induced hypertension via regulating neurotransmitters and cytokines in the hypothalamic paraventricular nucleus (PVN). Adult male Sprague-Dawley (SD) rats were fed with a normal salt diet (NS, 0.3% NaCl) or a high salt diet (HS, 8% NaCl) for 15 weeks to induce hypertension. These rats received CoQ10 (10 mg/kg/day) dissolved in olive oil was given by gavage (10 mg/kg/day) for 15 weeks. HS resulted in higher mean arterial pressure (MAP) and the sympathetic nerve activity (RSNA). These HS rats had higher PVN levels of norepinephrine (NE), tyrosine hydroxylase (TH), interleukin (IL)-1ß, NOX2 and NOX4, lower PVN levels of gamma-aminobutyric acid (GABA), IL-10, copper/zinc superoxide dismutase (Cu/Zn-SOD) and the 67-kDa isoform of glutamate decarboxylase (GAD67), as compared with NS group. CoQ10 supplementation reduced NE, TH, IL-1ß, NOX2 and NOX4 in the PVN, and induced IL-10, Cu/Zn-SOD and GAD67 in the PVN. These findings suggest that CoQ10 supplementation restores neurotransmitters and cytokines in the PVN, thereby attenuating high salt-induced hypertension.

Alpha lipoic acid supplementation attenuates reactive oxygen species in hypothalamic paraventricular nucleus and sympathoexcitation in high salt-induced hypertension.

AIMS: High salt-induced oxidative stress plays an important role in the development of hypertension. Alpha lipoic acid (ALA) is extensively recognized as having a powerful superoxide inhibitory property. In this study, we determined whether ALA supplementation attenuates oxidative stress in hypothalamic paraventricular nucleus (PVN), decreases the sympathetic activity and arterial pressure in high salt-induced hypertension by cross-talking with renin-angiotensin system (RAS) and pro-inflammatory cytokines (PICs). METHODS: Male Wistar rats were administered a normal-salt diet (NS, 0.3% NaCl) or a high-salt diet (HS, 8.0% NaCl) for 8 weeks. These rats received ALA (60mg/kg) dissolved in vehicle (0.9% saline) or an equal voleme of vehicle, by gastric perfusion for 9 weeks. RESULTS: High salt intake resulted in higher renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP). These rats also had higher levels of superoxide, gp91(phox), gp47(phox) (subunits of NAD(P)H oxidase), angiotensin-converting enzyme (ACE), angiotensin II type1 receptor (AT1-R), interleukin-1beta (IL-1ß), interleukin-6 (IL-6), and lower levels of interleukin-10 (IL-10) and copper/zinc superoxide dismutase (Cu/Zn-SOD) than control animals. Treatment with ALA significantly attenuated the levels of superoxide, gp91(phox), gp47(phox), ACE, AT1-R, IL-1ß and IL-6, increased the levels of IL-10 and Cu/Zn-SOD, and decreased MAP and RSNA compared with high-salt induced hypertensive rats. The mRNA expression of gp47(phox) and gp91(phox) are in accordance with their protein expression. CONCLUSION: These findings suggest that supplementation of ALA obviously decreases the sympathetic activity and arterial pressure in high salt-induced hypertension by improving the superoxide inhibitory property, suppressing the activation of RAS and restoring the balance between pro- and anti-inflammatory cytokines in the PVN.

Improving vagal activity ameliorates cardiac fibrosis induced by angiotensin II: in vivo and in vitro.

Cardiac remodeling is characterized by overactivity of the renin-angiotensin system (RAS) and withdrawal of vagal activity. We hypothesized that improving vagal activity could attenuate cardiac fibrosis induced by angiotensin II (Ang II) in vivo and in vitro. Rats were subjected to abdominal aorta constriction (AAC) with or without pyridostigmine (PYR) (31 mg/kg/d). After 8 weeks, PYR significantly decreased Ang II level, AT1 protein expression, and collagen deposition in cardiac tissue and improved heart rate variability, baroreflex sensitivity and cardiac function, which were abolished by atropine. In vitro, treatment of cardiac fibroblasts (CFs) with Ang II (10(-7) M) increased cell proliferation, migration, transformation, and secretory properties, which were significantly diminished by acetylcholine (ACh, 10(-6) M). Subsequently, Ang II significantly increased collagen type I expression as well as metalloproteinase (MMP)-2 expression and activity. Transforming growth factor (TGF)-ß1 expression and Smad3 phosphorylation presented a similar trend. Notably, the knockdown of the acetylcholine M2 receptor by siRNA could abolish ACh anti-fibrotic action. These data implicated cholinesterase inhibitor can increase vagal activity and reduce local Ang II level, and ACh inhibit Ang II pro-fibrotic effects. Our findings suggested that the parasympathetic nervous system can serve as a promising target for cardiac remodeling treatment.

[A new bisabolane-type sesquiterpenoid from Coreopsis tinctoria].

To study the chemical constituents of the inflorescences of Coreopsis tinctoria from Xinjiang, isolation and purification of constituents were carried out by column chromatography on macroporous resin (D101) , MCI gel, MDS gel, silica gel, Sephadex LH-20 and semi-preparative HPLC. The structures of the compounds were identified by physicchemical properties and spectral data analysis. Fourteen compounds were isolated and identified as coretinterpenoid A (1), coretinphenol (2), quercetin (3), quercetin-3-O-ß-glucopyranoside (4), luteolin (5), taxifolin (6), 7, 3', 5'-trihydroxyflavanone (7), isookanin (8), isookanin-7-O-ß-D-glucopyranoside (9), 5, 7, 3', 5'-tetrahydroxyflavanone-7-O-ß-D-glucopyranoside (10), butein (11), okanin (12), sulfuretin (13), and linocinnamarin (14). Compound 1 was a new isabolane-type sesquiterpenoid and compounds 4, 10 and 13 were isolated from this plant for the first time.

Discovery of potent and selective spiroindolinone MDM2 inhibitor, RO8994, for cancer therapy.

The field of small-molecule inhibitors of protein-protein interactions is rapidly advancing and the specific area of inhibitors of the p53/MDM2 interaction is a prime example. Several groups have published on this topic and multiple compounds are in various stages of clinical development. Building on the strength of the discovery of RG7112, a Nutlin imidazoline-based compound, and RG7388, a pyrrolidine-based compound, we have developed additional scaffolds that provide opportunities for future development. Here, we report the discovery and optimization of a highly potent and selective series of spiroindolinone small-molecule MDM2 inhibitors, culminating in RO8994.

Preclinical evaluation of the novel multi-targeted agent R1530.

PURPOSE: This study describes the antiproliferative activity of the multikinase inhibitor R1530 in vitro and its antitumor and anti-angiogenic activity, pharmacokinetics, and tolerability in vivo. METHODS: The antiproliferative activity of R1530 was investigated in a range of human tumor, endothelial and fibroblast cell lines. Tolerability and antitumor activity were assessed in mice bearing a range of human tumor xenografts, and anti-angiogenic properties were established in the murine corneal pocket assay. R1530 pharmacokinetics in mice were established. RESULTS: R1530 strongly inhibited human tumor cell proliferation. Growth factor-driven proliferation of endothelial and fibroblast cells was also inhibited. Significant tumor growth inhibition was demonstrated in a lung cancer xenograft model with a range of once daily, weekly and twice-weekly doses of R1530 (3.125-50 mg/kg qd, 100 mg/kg qw, 100 mg/kg biw). Daily doses were most effective in the lung cancer model and also had significant growth inhibitory effects in models of colorectal, prostate, and breast tumors. Tumor regression occurred in all models treated with the maximum tolerated daily dose (50 mg/kg). The doses of 25 and 50 mg/kg qd resulted in biologically significant increased survival in all tested models. After oral administration in nude mice, R1530 showed good tissue penetration. Exposure was dose dependent up to 100 mg/kg with oral administration. CONCLUSIONS: R1530 has demonstrated activity against a range of tumor models in vitro and in vivo and is an effective inhibitor of angiogenesis. These findings support the approach of targeting multiple pathways in the search for potential agents with improved anticancer properties.

[Effects of selenium and/or iodine deficiency on chondrocyte apoptosis in rats].

OBJECTIVE: To explore the effects of selenium and/or iodine deficiency on chondrocyte apoptosis in articular cartilage in rats. METHODS: Forty-eight Sprague-Dawley rats were randomly divided into selenium deficiency group, iodine deficiency group, combined selenium and iodine deficiency group, and control group. Chondrocyte apoptosis was detected by terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling (TUNEL) method, and Bcl-2 and Bax in articular cartilage were stained by immunohistochemistry in F3 generation of rats. RESULTS: In articular cartilage, the positive rate of apoptotic chondrocytes stained by TUNEL in the upper and middle zones in selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05) were significantly higher than that in control group. The apoptotic chondrocytes were prominent in the middle zone. The positive percentage of chondrocytes apoptosis was not significantly different among these three groups (P > 0.05). Compared with the control group, the expressions of both Bcl-2 and Bax were significantly higher in the upper and middle zone in the selenium deficiency group, iodine deficiency group, and combined selenium and iodine deficiency group (all P < 0.05); however, the expressions of Bcl-2 and Bax were not significantly different among these three groups (P > 0.05). CONCLUSION: Selenium and/or iodine deficiency may induce chondrocyte apoptosis.

A correction method for nonlinear artifacts in CT imaging.

This work presents a new method to reduce nonlinear artifacts in computed tomography (CT). Based on the traditional water-equivalent beam hardening correction method, a new systematic iterative algorithm has been designed to modify the original spectrum, which is under the influences of certain added filter materials and some unknown factors. By incorporating the characters of polychromatic beam hardening and the insensibility and nonuniformity of detectors into consideration, a new polynomial function curve is calculated. The curve can calibrate CT raw data and reduce the nonlinear artifacts, such as shading artifacts, dark artifacts, cupping artifacts and ring artifacts, in soft tissue. Comparing with the traditional water-equivalent correction, results show that this method can significantly improve the image quality. Meanwhile, the method is pre-processing and will not increase the normal reconstruction time. That is, all the time-consuming works can be done before scanning patients. However, it is still depending on the size of phantoms currently used, and more detailed works need to be done in the future.