Comparison of nutritional supplements in improving glycolipid metabolism and endocrine function in polycystic ovary syndrome: a systematic review and network meta-analysis.

Objective: To explore the comparative effectiveness of nutritional supplements in improving glycolipid metabolism and endocrine function in patients with polycystic ovary syndrome (PCOS). Method: Randomized controlled clinical trials on the effects of nutritional supplements in PCOS patients were searched in PubMed, Embase, Cochrane Library, and Web of Science from their establishments to March 15, 2023. Then, literature screening, data extraction, and network meta-analysis were performed. This study was registered at PROSPERO (registration number CRD 42023441257). Result: Forty-one articles involving 2,362 patients were included in this study. The network meta-analysis showed that carnitine, inositol, and probiotics reduced body weight and body mass index (BMI) compared to placebo, and carnitine outperformed the other supplements (SUCRAs: 96.04%, 97.73%, respectively). Omega-3 lowered fasting blood glucose (FBG) (SUCRAs: 93.53%), and chromium reduced fasting insulin (FINS) (SUCRAs: 72.90%); both were superior to placebo in improving insulin resistance index (HOMA-IR), and chromium was more effective than Omega-3 (SUCRAs: 79.99%). Selenium was potent in raising the quantitative insulin sensitivity index (QUICKI) (SUCRAs: 87.92%). Coenzyme Q10 was the most effective in reducing triglycerides (TG), total cholesterol (TC), and low-density lipoprotein cholesterol (LDL-C) levels (SUCRAs: 87.71%, 98.78%, and 98.70%, respectively). Chromium and probiotics decreased TG levels, while chromium and vitamin D decreased TC levels. No significant differences were observed in high-density lipoprotein cholesterol (HDL-C), total testosterone (TT), sex-hormone binding globulin (SHBG), and C-reactive protein (CRP) between nutritional supplements and placebo. Conclusion: Carnitine was relatively effective in reducing body mass, while chromium, Omega-3, and selenium were beneficial for improving glucose metabolism. Meanwhile, coenzyme Q10 was more efficacious for improving lipid metabolism. However, publication bias may exist, and more high-quality clinical randomized controlled trials are needed.

Effect of low-calcium and standard-calcium dialysate on serum calcium, phosphorus and full-segment parathyroid hormone in patients on peritoneal dialysis: A retrospective observational study.

OBJECTIVE: To investigate the effects of low-calcium and standard-calcium dialysate in patients with chronic kidney disease on peritoneal dialysis, and find out which dialysate has less vascular calcification effect. METHODS: A total of 141 patients who had undergone peritoneal dialysis (PD) for 2 years in the PD centre from January 2012 to December 2017 were included and divided into two groups according to the calcium concentration of the PD fluid used. There were 79 cases in the low-calcium group, with a dialysate calcium concentration of 1.25 mmol/L and 62 cases in the standard-calcium group, with a dialysate calcium concentration of 1.75 mmol/L. The demographic characteristics and clinical information before initiation of PD were collected and compared between the two groups. Information on the serum calcium, phosphorus and PTH, systolic and diastolic blood pressures and the use of antihypertensive and phosphate-lowering drugs in the second year of dialysis was also collected and compared between the two groups. Vascular calcification was assessed in patients on PD treatment. RESULTS: The mean serum calcium concentrations before initiation of PD in the low- and standard-calcium groups were 1.94 ± 0.27 and 1.89 ± 0.28 mmol/L, respectively. The serum calcium concentrations after PD were 2.30 ± 0.21 and 2.41 ± 0.23 mmol/L, respectively. After PD, the serum calcium concentration in both groups was significantly increased (p < 0.05). The serum calcium concentration in the low-calcium group after PD treatment was lower than that in the standard-calcium group, and the difference was statistically significant (p < 0.05). Compared with the standard-calcium group, patients in the low-calcium group had significantly higher parathyroid hormone concentrations (p < 0.05). More types of phosphate-lowering drugs were used (59.49%) in the low-calcium group than that in the standard-calcium group (35.48%; p < 0.05). The number of antihypertensive drug usage were also higher in the low-calcium group, and the difference was statistically significant (p < 0.05). As for the vascular calcification effect, the two groups have shown no statistical difference in abdominal aortic calcification rate, carotid arteriosclerosis rate and aortic arch calcification rate (p < 0.05). CONCLUSION: We found that low-calcium PD fluid may increase the PTH level and the proportion of CKD patients using antihypertensive drug and phosphorus-lowering drug, but the vascular calcification effect of the low and standard calcium PD fluid needs further exploration. This paper provides new evidence for the choice of dialysate for PD, low-calcium dialysate has no outstanding advantages for long term dialysis.

Network pharmacology identification and in Vivo validation of key pharmacological pathways of Phyllanthus reticulatus (Euphorbiaceae) leaf extract in liver cancer treatment.

ETHNOPHARMACOLOGICAL RELEVANCE: Phyllanthus reticulatus (Euphorbiaceae) is a medicinal plant that has been used in Zhuang medicine since ancient times. Traditionally, it has the effect of removing toxins and detumescence and can be used to treat hepatitis in China and India. Our previous studies have proved that the ethyl acetate extract of its leaves (PRPE) has an anti-hepatoma effect. AIM OF THE STUDY: To predict targets of an ethyl acetate extract of Phyllanthus reticulatus leaves (PRPE) in hepatoma treatment via network pharmacology and verify the predictions in a mouse model of liver cancer. MATERIALS AND METHODS: Chemical constituents and therapeutic targets of P. reticulatus (PRP) were searched and predicted via public databases. A protein-protein interaction network comprising common targets was constructed, and the key gene targets were identified. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were used for biological function and pathway enrichment analyses. The effects of PRP on BEL-7404 and HepG2 cells were determined by MTT assay, apoptosis was measured by flow cytometry and hoechst44432/PI. And a nude mouse xenograft model was established to verify the anti-tumour effect in vivo. The histopathology of tumours was observed by staining with haematoxylin and eosin (H&E). Reverse transcription-polymerase chain reaction (RT-PCR) and immunohistochemistry were used to determine the gene and protein expression levels of phosphoinositide 3-kinase (PI3K), Akt1, p53, caspase-3, Bcl-2 and Bax, respectively. RESULTS: Twenty-seven chemical components and 567 potential therapeutic targets of PRP were identified. GO analysis indicated that these targets are mainly associated with peptidyl-tyrosine phosphorylation and steroid metabolic process. KEGG analysis showed that the targets are mainly located in the PI3K/Akt, apoptosis, mitogen-activated protein kinase (MAPK), Ras and vascular endothelial growth factor (VEGF) signalling pathways. According to the p-adjust value, the PI3K/Akt pathway is the core pathway. In vitro, PRPE could inhibit proliferation and induce apoptosis in hepatoma cells. IC50 values of PRPE were 2.48 and 6.34 mg/mL for BEL-7404 and hepG2 cells, respectively. PRPE significantly reduced tumour volume and weight. H&E results showed that PRPE repaired necrotic areas in hepatoma cells. PRPE reduced the protein expression of PI3K, Akt1 and Bcl-2 and increased the protein expression of p53 and Bax. Meanwhile, PRPE reduced the mRNA expression of PI3K, AKT1 and BCL2 and increased the mRNA expression of TP53, CASP3 and BAX. CONCLUSION: The targets of PRPE are the PI3K/Akt, apoptosis, MAPK, Ras and VEGF signalling pathways. Passing through the PI3K/Akt pathway to induce apoptosis is the main mechanism of PRPE.

Photo-Enhanced Chemotherapy Performance in Bladder Cancer Treatment via Albumin Coated AIE Aggregates.

The implementation of cisplatin-based neoadjuvant chemotherapy (NAC) plays a key role in conjunction with surgical resection in preventing bladder cancer progression and recurrence. However, the significant dose-dependent toxic side effects of NAC are still a major challenge. To solve this problem, we developed a photoenhanced cancer chemotherapy (PECC) strategy based on AIEgen ((E)-3-(2-(2-(5-(4-(diphenylamino)phenyl)thiophen-2-yl)vinyl)-1,1-dimethyl-1H-3λ4-benzo[e]indol-3-yl)propane-1-sulfonate), which is abbreviated as BITT. Multifunctional BITT@BSA-DSP nanoparticles (NPs) were employed with an albumin-based nanocarrier decorated with the cisplatin(IV) prodrug and loaded to produce strong near-infrared fluorescence imaging (NIR FLI), and they exhibited good photoenhancement performance via photodynamic therapy (PDT) and photothermal therapy (PTT). In vitro results demonstrated that BITT@BSA-DSP NPs could be efficiently taken up by bladder cancer cells and reduced to release Pt (II) under reductase, ensuring the chemotherapy effect. Furthermore, both in vitro and in vivo evaluation verified that the integration of NIR FL imaging-guided PECC efficiently promoted the sensitivity of bladder cancer to cisplatin chemotherapy with negligible side effects. This work provides a promising strategy to enhance the sensitivity of multiple cancers to chemotherapy drugs and even achieve effective treatments for drug-resistant cancers.

Anti-Inflammatory, Barrier-Protective, and Antiwrinkle Properties of Agastache rugosa Kuntze in Human Epidermal Keratinocytes.

This work aimed to assess the skin-beneficial properties of Agastache rugosa Kuntze, an herbal medication used to treat different types of disorders in traditional folk medicine. The total phenolic compounds and total antiradical, nitrite scavenging, superoxide scavenging, antielastase, and antihyaluronidase activities of a hot water extract of A. rugosa Kuntze leaves (ARE) were spectrophotometrically determined. Intracellular reactive oxygen species (ROS) was fluorometrically quantitated using 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA). Inducible nitric oxide synthase (iNOS) and filaggrin were evaluated using Western analysis. Real-time quantitative RT-PCR was used to measure filaggrin mRNA. Caspase-14 activity was determined using a fluorogenic substrate. ARE contained the total phenolic content of 38.9 mg gallic acid equivalent/g extract and exhibited 2,2'-diphenyl-1-picrylhydrazyl (DPPH) radical, superoxide radical, and nitrite scavenging activities with the SC50 values of 2.9, 1.4, and 1.7 mg/mL, respectively. ARE exerted suppressive activities on nitric oxide (NO) and ROS levels elevated by lipopolysaccharide (LPS) or tumor necrosis factor-α (TNF-α) in HaCaT keratinocytes. It attenuated the LPS-stimulated expression of iNOS. ARE augmented the UV-B-reduced filaggrin expression on both protein and mRNA levels and was capable of upregulating the UV-B-reduced caspase-14 activity. ARE inhibited in vitro elastase and hyaluronidase activities associated with the wrinkling process. ARE, at the concentrations used, did not interfere with the viability of HaCaT keratinocytes. These findings preliminarily imply that the leaves of A. rugosa possess desirable cosmetic potentials, such as anti-inflammatory, barrier protective, and antiwrinkle activities, which infers their skin healing potentials.

Efficacy of clomifene citrate combined Bushen Culuan Decoction for the treatment of infertility caused by polycystic ovary syndrome: A protocol of systematic review.

BACKGROUND: The aim of this study is to assess the efficacy and safety of clomifene citrate combined Bushen Culuan Decoction (CCBCD) in treating infertility caused by polycystic ovary syndrome (PCOS). METHODS: We will carry out this study to identify eligible randomized controlled trials (RCTs) in Cochrane Library, PUBMED, EMBASE, Web of Science, CINAHL, and China National Knowledge Infrastructure from inception to the present. There are no limitations to the language and publication time. We will perform study selection, data extraction, and study quality assessment. If possible, a meta-analysis will be developed to judge the comparative efficacy and safety of CCBCD with other treatments. RESULTS: The results of this study will summarize current high quality RCTs to provide direct evidence of CCBCD in treating infertility in patients with PCOS. CONCLUSION: This study may provide evidence to determine whether CCBCD is effective and safe or not for the treatment of infertility caused by PCOS. STUDY REGISTRATION: INPLASY202050090.

Targeting translation initiation by synthetic rocaglates for treating MYC-driven lymphomas.

MYC-driven lymphomas, especially those with concurrent MYC and BCL2 dysregulation, are currently a challenge in clinical practice due to rapid disease progression, resistance to standard chemotherapy, and high risk of refractory disease. MYC plays a central role by coordinating hyperactive protein synthesis with upregulated transcription in order to support rapid proliferation of tumor cells. Translation initiation inhibitor rocaglates have been identified as the most potent drugs in MYC-driven lymphomas as they efficiently inhibit MYC expression and tumor cell viability. We found that this class of compounds can overcome eIF4A abundance by stabilizing target mRNA-eIF4A interaction that directly prevents translation. Proteome-wide quantification demonstrated selective repression of multiple critical oncoproteins in addition to MYC in B-cell lymphoma including NEK2, MCL1, AURKA, PLK1, and several transcription factors that are generally considered undruggable. Finally, (-)-SDS-1-021, the most promising synthetic rocaglate, was confirmed to be highly potent as a single agent, and displayed significant synergy with the BCL2 inhibitor ABT199 in inhibiting tumor growth and survival in primary lymphoma cells in vitro and in patient-derived xenograft mouse models. Overall, our findings support the strategy of using rocaglates to target oncoprotein synthesis in MYC-driven lymphomas.

Ginsenoside Rg1 Prevents Chemotherapy-Induced Cognitive Impairment: Associations with Microglia-Mediated Cytokines, Neuroinflammation, and Neuroplasticity.

Chemotherapy-induced cognitive impairment, also known as "chemobrain," is a common side effect. The purpose of this study was to examine whether ginsenoside Rg1, a ginseng-derived compound, could prevent chemobrain and its underlying mechanisms. A mouse model of chemobrain was developed with three injections of docetaxel, adriamycin, and cyclophosphamide (DAC) in combination at a 2-day interval. Rg1 (5 and 10 mg/kg daily) was given 1 week prior to DAC regimen for 3 weeks. An amount of 10 mg/kg Rg1 significantly improved chemobrain-like behavior in water maze test. In vivo neuroimaging revealed that Rg1 co-treatment reversed DAC-induced decreases in prefrontal and hippocampal neuronal activity and ameliorated cortical neuronal dendritic spine elimination. It normalized DAC-caused abnormalities in the expression of multiple neuroplasticity biomarkers in the two brain regions. Rg1 suppressed DAC-induced elevation of the proinflammatory cytokines tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), but increased levels of the anti-inflammatory cytokines IL-4 and IL-10 in multiple sera and brain tissues. Rg1 also modulated cytokine mediators and inhibited DAC-induced microglial polarization from M2 to M1 phenotypes. In in vitro experiments, while impaired viability of PC12 neuroblastic cells and hyperactivation of BV-2 microglial cells, a model of neuroinflammation, were observed in the presence of DAC, Rg1 co-treatment strikingly reduced DAC's neurotoxic effects and neuroinflammatory response. These results indicate that Rg1 exerts its anti-chemobrain effect in an association with the inhibition of neuroinflammation by modulating microglia-mediated cytokines and the related upstream mediators, protecting neuronal activity and promoting neuroplasticity in particular brain regions associated with cognition processing.

Probiotic fermentation augments the skin anti-photoaging properties of Agastache rugosa through up-regulating antioxidant components in UV-B-irradiated HaCaT keratinocytes.

BACKGROUND: Agastache rugosa (Fisch. & C.A.Mey.) Kuntze (Korean mint) is used to treat diverse types of human disorders in traditional medicine. In recent years, its non-fermented leaf extract (ARE) has been shown to possess protective properties against ultraviolet-B (UV-B) radiation-induced photooxidative stress. The present work aimed to examine whether probiotic bacterial fermentation would potentiate the skin anti-photoaging activity of ARE or not, by comparing the protective properties of ARE and corresponding fermented extract (ARE-F) against UV-B radiation-induced photooxidative stress in HaCaT keratinocytes. METHODS: ARE-F was produced from ARE by the fermentation with Lactobacillus rhamnosus HK-9, a type of Gram-positive probiotic bacterial strain. Anti-photoaging activities were evaluated by analyzing reactive oxygen species (ROS), promatrix metalloproteinases (proMMPs), total glutathione (GSH) and total superoxide dismutase (SOD) in UV-B-irradiated HaCaT keratinocytes. Antiradical activity was determined using 2,2-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) radical scavenging assay. RESULTS: ARE-F contained higher attenuating activity on the UV-B-induced ROS generation than ARE. Similarly, ARE-F was able to diminish the UV-B-induced proMMP-9 and -2 more effectively than ARE. ARE-F displayed higher tendencies to augment the UV-B-reduced total GSH content and SOD activity than ARE. However, there were no significant difference between ARE and ARE-F in ABTS radical scavenging activities. CONCLUSIONS: The findings suggest that the UV-B radiation-protective activity of ARE is enhanced by probiotic bacterial fermentation, which might improve the therapeutic and cosmetic values of A. rugosa leaves.

Effects of Chinese Dietary Pattern of Fat Content, n-6/n-3 Polyunsaturated Fatty Acid Ratio, and Cholesterol Content on Lipid Profile in Rats.

This study aims to investigate the effect of Chinese diet pattern of fat content (30% or 36.06%), n-6/n-3 polyunsaturated fatty acid (PUFA) ratio (5 : 1 or 9 : 1), and cholesterol content (0.04 or 0.057 g/kg total diet) on lipid profile using a rat model. Results showed that rats' body weights (BWs) were controlled by the simultaneous intakes of cholesterol level of 0.04 g/kg total diet and n-6/n-3 ratio of 5 : 1. In addition, under high-fat diet, increased cholesterol feeding led to increased total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C) levels and decreased triacylglycerols (TG) in rats' plasma. However, high density lipoprotein cholesterol (HDL-C) level and the ratios of HDL-C/LDL-C and HDL-C/TC in rats' plasma increased in response to simultaneous intakes of low n-6/n-3 ratio (5 : 1) and cholesterol (0.04 g/kg total diet) even under high-fat diet. Moreover, as the n-6/n-3 PUFA ratio in the diet decreased, the proportion of n-3 PUFAs increased in plasma, liver, and muscle and resulted in the decrease of n-6/n-3 PUFA ratio.

Protective properties of geniposide against UV-B-induced photooxidative stress in human dermal fibroblasts.

CONTEXT: Geniposide (genipin-1-O-ß-d-glucoside) is a major bioactive ingredient in the fruits of gardenia [Gardenia jasminoides J. Ellis (Rubiaceae)], a traditional herbal medicine in Asian countries. OBJECTIVE: This work assesses the skin anti-photoaging potential of geniposide in human dermal fibroblasts under UV-B irradiation. MATERIALS AND METHODS: The anti-photoaging property of geniposide, at varying concentrations (5, 12 and 30 µM) treated for 30 min prior to UV-B irradiation, was evaluated by analysing reactive oxygen species (ROS), promatrix metalloproteinase-2 (proMMP-2), glutathione (GSH), superoxide dismutase (SOD), nuclear factor erythroid 2-related factor 2 (Nrf2) and cellular viability. RESULTS: Geniposide suppressed the ROS elevation under UV-B irradiation, which was revealed using three ROS-sensitive fluorescent dyes. The use of 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA), dihydroethidium (DHE) and dihydrorhodamine 123 (DHR-123) elicited the IC50 values of 10.5, 9.8 and 21.0 µM, respectively. Geniposide attenuated proMMP-2 at activity and protein levels that were elevated under UV-B-irradiation. Geniposide at 5, 12 and 30 µM augmented the UV-B-reduced total GSH content to 1.9 ± 0.1-, 2.2 ± 0.2- and 4.1 ± 0.2-fold, respectively. Geniposide at 5, 12 and 30 µM upregulated total SOD activity to 2.3 ± 0.1-, 2.5 ± 0.3- and 3.3 ± 0.3-fold, respectively, under UV-B irradiation. The UV-B-reduced Nrf2 levels were also upregulated by geniposide treatment. Geniposide, at the concentrations used, was unable to interfere with cellular viabilities under UV-B irradiation. DISCUSSION AND CONCLUSIONS: After the skin anti-photoaging potential of geniposide may be further verified, it can be utilized as a safer resource in the manufacture of effective anti-aging cosmetics.

Fermented Platycodon grandiflorum Extract Inhibits Lipid Accumulation in 3T3-L1 Adipocytes and High-Fat Diet-Induced Obese Mice.

The aim of this study was to investigate whether fermented Platycodon grandiflorum (FPG) inhibits lipid accumulation in 3T3-L1 adipocytes and mice with high-fat diet (HFD)-induced obesity. We evaluated the effect of FPG on antiadipogenic activity via regulation of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα), as well as protein expression of their target genes, fatty acid binding protein 4 (FABP4). We further examined the antiobesity effects of FPG on HFD-induced obesity in mice. The FPG was orally administered to mice with a HFD at 50, 100, or 200 mg/kg/day for 8 weeks. Our results show that FPG significantly inhibited fat accumulation during 3T3-L1 adipogenesis through downregulating adipogenic transcript factors. Moreover, FPG markedly reduced the final body weight with a decrease in epididymal adipose tissue mass and adipocyte size compared with the untreated HFD-induced group. The effects of FPG on HFD-induced obesity were primarily responsible for inhibiting adipogenesis in adipose tissue and regulating lipid metabolism, such as through lipogenesis and fatty acid oxidation. Additionally, FPG ameliorated serum total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels. Hence, FPG may be an alternative treatment for controlling obesity through downregulating lipid accumulation.

Attenuating properties of Agastache rugosa leaf extract against ultraviolet-B-induced photoaging via up-regulating glutathione and superoxide dismutase in a human keratinocyte cell line.

Agastache rugosa Kuntze, known as a Korean mint, is an herbal medicine that has been used for the treatment of diverse kinds of symptoms in traditional medicine. This work was undertaken to assess the protective properties of A. rugosa leaves against UV-B-induced photoaging in HaCaT keratinocytes. They were evaluated via analyzing reactive oxygen species (ROS), promatrix metalloproteinase-2 (proMMP-2) and -9 (proMMP-9), total glutathione (GSH), total superoxide dismutase (SOD), cellular viability, flavonoid content and in vitro radical scavenging activity. Total flavonoid content of ARE, a hot water extract of A. rugosa leaves, was 22.8±7.6mg of naringin equivalent/g ARE. ARE exhibited ABTS(+) radical scavenging activity with an SC50 of 836.9µg/mL. ARE attenuated the UV-B-induced ROS generation. It diminished the UV-B-induced elevation of proMMP-2 and -9 at both activity and protein levels. On the contrary, ARE was able to enhance the UV-B-reduced total GSH and total SOD activity levels. ARE, at the used concentrations, was unable to interfere with the cellular viabilities of HaCaT keratinocytes under UV-B irradiation. Taken together, ARE possesses a protective potential against UV-B-induced photoaging in HaCaT keratinocytes, possibly based upon up-regulating antioxidant components, including total GSH and SOD. These findings reasonably suggest the use of A. rugosa leaves as a photoprotective resource in manufacturing functional cosmetics.

Celsr3 and Fzd3 Organize a Pioneer Neuron Scaffold to Steer Growing Thalamocortical Axons.

Celsr3 and Fzd3 regulate the development of reciprocal thalamocortical projections independently of their expression in cortical or thalamic neurons. To understand this cell non autonomous mechanism further, we tested whether Celsr3 and Fzd3 could act via Isl1-positive guidepost cells. Isl1-positive cells appear in the forebrain at embryonic day (E) 9.5-E10.5 and, from E12.5, they form 2 contingents in ventral telencephalon and prethalamus. In control mice, corticothalamic axons run in the ventral telencephalic corridor in close contact with Isl1-positive cells. When Celsr3 or Fzd3 is inactivated in Isl1-expressing cells, corticofugal fibers stall and loop in the ventral telencephalic corridor of high Isl1 expression, and thalamic axons fail to cross the diencephalon-telencephalon junction (DTJ). At E12.5, before thalamic and cortical axons emerge, pioneer projections from Isl1-positive cells cross the DTJ from both sides in control but not mutant embryos. These early projections appear to act like a bridge to guide later growing thalamic axons through the DTJ. Our data suggest that Celsr3 and Fzd3 orchestrate the formation of a scaffold of pioneer neurons and their axons. This scaffold extends from prethalamus to ventral telencephalon and subcortex, and steers reciprocal corticothalamic fibers.

Lichong decoction reduces Matrix Metalloproteinases-2 expression but increases Tissue Inhibitors of Matrix Metalloproteinases-2 expression in a rat model of uterine leiomyoma.

OBJECTIVE: To study the effect of Lichong decoction (LD) on expression of matrix metalloproteinase- 2 (MMP-2) and metalloproteinase-2 (TIMP-2) in a rat model of uterine leiomyoma (UL). METHODS: UL was induced in rats using exogenous estrogen and progesterone. LD was administered (p.o.) for 4 weeks, and mifepristone (RU-486) used as a control. To observe the effect of LD on the uterine coefficient and uterine transverse diameter, a radioimmunoassay method was used to detect serum levels of sex hormones. Light microscopic analyses of pathologic changes in the tissues of UL rats were evaluated. Expression of the proteins of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in uterine tissues was assessed by immunohistochemical staining and western blotting. RESULTS: A UL model in rats was established successfully. LD reduced uterine weight, uterine coefficient, and uterine transverse diameter compared with untreated controls. LD reduced levels of estradiol, progesterone, follicle-stimulating hormone, and luteinizing hormone in our UL models. LD improved the pathologic condition of uterine muscle. Expression of MMP-2 protein decreased to varying extents in LD-treated groups, but TIMP-2 levels were enhanced. LD appears to reduce MMP-2 expression and increase TIMP-2 expression in UL tissue. CONCLUSION: These data suggest that the mechanism of action of LD on ULs may involve reduction of MMP-2 expression and increase in TIMP-2 expression in rats.

Anti-Diabetic Effect of Aster sphathulifolius in C57BL/KsJ-db/db Mice.

In this study, we investigated the anti-diabetic effect of Aster sphathulifolius (AS) extract in C57BL/KsJ-db/db mice. The db/db mice were orally administered with AS 50% ethanol extract at concentrations of 50, 100, and 200 mg/kg/day (db/db-AS50, db/db-AS100, and db/db-AS200, respectively) for 10 weeks. Food and water intake, fasting blood glucose concentrations, blood glycosylated hemoglobin levels, and plasma insulin levels were significantly lower in the db/db-AS200 group than in the vehicle-treated db/db group; whereas glucose tolerance was significantly improved in the db/db-AS200 group. Moreover, AS dose dependently increased both insulin receptor substrate 1 and glucose transporter type 4 expression in skeletal muscle, significantly increased glucokinase expression, and decreased glucose 6-phosphatase and phosphoenolpyruvate carboxykinase expressions in the liver. The expressions of transcription factors, such as sterol-regulatory element-binding protein, peroxisome proliferator-activated receptor γ, and adipocyte protein 2, were upregulated in adipose tissue. Furthermore, immunohistochemical analysis showed that AS upregulated insulin production by increasing pancreatic ß-cell mass. In summary, AS extract normalized hyperglycemia by multiple mechanisms: inhibition of glyconeogenesis, acceleration of glucose metabolism and lipid metabolism, and increase of glucose uptake. Using in vivo assays, this study has shown the potential of AS as a medicinal food and suggests the efficacy of AS for the use of prevention of diabetes.

Genetic evidence that Celsr3 and Celsr2, together with Fzd3, regulate forebrain wiring in a Vangl-independent manner.

Celsr3 and Fzd3, members of "core planar cell polarity" (PCP) genes, were shown previously to control forebrain axon guidance and wiring by acting in axons and/or guidepost cells. Here, we show that Celsr2 acts redundantly with Celsr3, and that their combined mutation mimics that of Fzd3. The phenotypes generated upon inactivation of Fzd3 in different forebrain compartments are similar to those in conditional Celsr2-3 mutants, indicating that Fzd3 and Celsr2-3 act in the same population of cells. Inactivation of Celsr2-3 or Fzd3 in thalamus does not affect forebrain wiring, and joint inactivation in cortex and thalamus adds little to cortical inactivation alone in terms of thalamocortical projections. On the other hand, joint inactivation perturbs strongly the formation of the barrel field, which is unaffected upon single cortical or thalamic inactivation, indicating a role for interactions between thalamic axons and cortical neurons in cortical arealization. Unexpectedly, forebrain wiring is normal in mice defective in Vangl1 and Vangl2, showing that, contrary to epithelial PCP, axon guidance can be Vangl independent in some contexts. Our results suggest that Celsr2-3 and Fzd3 regulate axonal navigation in the forebrain by using mechanisms different from classical epithelial PCP, and require interacting partners other than Vangl1-2 that remain to be identified.

Discovery of an irreversible HCV NS5B polymerase inhibitor.

The discovery of lead compound 2e was described. Its covalent binding to HCV NS5B polymerase enzyme was investigated by X-ray analysis. The results of distribution, metabolism and pharmacokinetics were reported. Compound 2e was demonstrated to be potent (replicon GT-1b EC50 = 0.003 µM), highly selective, and safe in in vitro and in vivo assays.

Quantum dot imaging for HSP70 and HSF­1 kinetics in SCC­25 cells with or without leucine deprivation following heat shock.

The aim of this study was to develop a quantum dot-based approach for heat shock protein 70 (HSP70) and heat shock factor 1 (HSF-1) kinetics following heat shock, and to discover approaches to thermotherapy based on disrupting the effect of activation of HSF-1 and the accumulation of HSP70 by leucine deprivation. SCC-25 cells cultured with limiting leucine or normal leucine were stressed at 42˚C for 30 min, and were cultured for 2, 4, 6, 8 and 10 h, respectively. The expression of HSP70 and HSF-1 was observed using confocal laser microscopy and semi-quantitative analysis was performed by Image-Pro Plus. At 6 h after heating, HSF-1 in cells cultured with normal leucine was activated and translocated from the cytosol to the nucleus, and the synthesis of HSP70 reached the maximum value and had a tendency to gather in the nucleus. However, in cells cultured with limiting leucine, HSF-1 activity decreased and accumulation of HSP70 was not found. Leucine deprivation results in the inactivation of HSF-1 leading to slight accumulation of HSP70 and no tendency to gather in the nucleus. Thus, HSF-1 may serve as a novel therapeutic target in the treatment of oral cancer.

Bone morphogenetic protein-2 expression in spinal fusion masses enhanced by extracorporeal shock wave treatment: a rabbit experiment.

PURPOSE: Extracorporeal shock wave (ESW) has been introduced to enhance spinal fusion. This study was conducted to assess the effect of ESW on bone morphogenetic protein-2 (BMP-2) expression in a spinal fusion experiment. METHODS: Twelve rabbits underwent fusion at bilateral L5-6 intertransverse spaces. They were evenly divided into two groups. In the study group, bilateral L5 and L6 transverse processes were treated with 1,000 impulses of ESW at 14 kV at 12 weeks. In the control group, the rabbits did not receive ESW treatment. All rabbits were sacrificed at 16 weeks, and their lumbar spines were harvested for radiographic and molecular biological study. RESULTS: In the study group (n = 6), the radiographs showed good fusion in all six rabbits, while in the control group (n = 6), good fusion was found only in three rabbits (50%). Although more rabbits in the study group had a good fusion result, the inter-group difference was not statistically significant (P = 0.182). In the molecular biological examination, the mean value of the normalized expression of BMP-2 mRNA in the fusion masses of the study group was 90 ± 8.4 while that of the control group was 77.33 ± 6.74. Statistical analysis showed the study group had a significantly higher BMP-2 mRNA expression in the fusion masses than the control group (P = 0.018). CONCLUSIONS: The current study showed that ESW treatment enhances BMP-2 mRNA expression in spinal fusion masses.