Sinapic acid modulates oxidative stress and metabolic disturbances to attenuate ovarian fibrosis in letrozole-induced polycystic ovary syndrome SD rats.

Sinapic acid (SA) is renowned for its many pharmacological activities as a polyphenolic compound. The cause of polycystic ovary syndrome (PCOS), a commonly encountered array of metabolic and hormonal abnormalities in females, has yet to be determined. The present experiment was performed to evaluate the antifibrotic properties of SA in rats with letrozole-induced PCOS-related ovarian fibrosis. SA treatment successfully mitigated the changes induced by letrozole in body weight (BW) (p < .01) and relative ovary weight (p < .05). Histological observation revealed that SA reduced the number of atretic and cystic follicles (AFs) and (CFs) (p < .01), as well as ovarian fibrosis, in PCOS rats. Additionally, SA treatment impacted the serum levels of sex hormones in PCOS rats. Luteinizing hormone (LH) and testosterone (T) levels were decreased (p < .01, p < .05), and follicle-stimulating hormone (FSH) levels were increased (p < .05). SA administration also decreased triglyceride (TG) (p < .01) and total cholesterol (TC) levels (p < .05) and increased high-density lipoprotein cholesterol (HDL-C) levels (p < .01), thereby alleviating letrozole-induced metabolic dysfunction in PCOS rats. Furthermore, SA treatment targeted insulin resistance (IR) and increased the messenger RNA (mRNA) levels of antioxidant enzymes in the ovaries of PCOS rats. Finally, SA treatment enhanced the activity of peroxisome proliferator-activated receptor-γ (PPAR-γ), reduced the activation of transforming growth factor-ß1 (TGF-ß1)/Smads, and decreased collagen I, α-smooth muscle actin (α-SMA), and connective tissue growth factor (CTGF) levels in the ovaries of PCOS rats. These observations suggest that SA significantly ameliorates metabolic dysfunction and oxidative stress and ultimately reduces ovarian fibrosis in rats with letrozole-induced PCOS.

Koumine ameliorates neuroinflammation by regulating microglia polarization via activation of Nrf2/HO-1 pathway.

BACKGROUND: Gelsemium elegans (Gardner & Chapm.) Benth (G. elegans) has been widely used as a traditional folk medicine in China and Southeast Asia. As the most abundant alkaloid in G. elegans, Koumine (KM) has been revealed the effect of inflammatory attenuation modulating by macrophage activation and polarization. PURPOSE: This study aimed to explore the effect of KM on modulation of microglia polarization that led to the suppression of neuroinflammation and further improved neurodegenerative behavior. METHODS: Inflammatory mediators, microglia M1 and M2 phenotype markers and Nrf2/HO-1 pathway related protein were assessed in LPS-induced BV2 cells and LPS-treated mice by RT-PCR, immunohistochemistry, immunofluorescence and Western blotting. Moreover, the learning and memory abilities of mice were evaluated by Morris water maze test, and the neuronal damage was evaluated by the Nissl staining. RESULTS: KM attenuated LPS-induced viability and morphological changes in BV2 microglial cells. Our findings showed that KM activated the Nrf2/HO-1 signaling pathway to promote phenotypic switch from M1 to M2 phenotypes. This switch suppresses the release of inflammatory mediators in LPS-induced BV2 cells. Meanwhile, KM attenuated neuroinflammation through modulating microglia polarization and subsequently reversed the behavioral alterations in LPS-induced mice model of neuroinflammation. CONCLUSIONS: KM may alleviate neuroinflammation by regulating microglia polarization with the involvement of Nrf2/HO-1 pathway, resulting of the neuroprotective effect.

Irpex lacteus polysaccharide exhibits therapeutic potential for ovarian fibrosis in PCOS rats via the TGF-ß1/smad pathway.

Polycystic ovarian syndrome (PCOS) is one of the commonest endocrinopathies in childbearing women. The research was conducted to assess the impact of Irpex lacteus polysaccharide (ILP, 1000 mg/kg) on the letrozole (1 mg/kg)-induced PCOS model in female rats. Metformin (Met, 265 mg/kg) as the positive control. The study suggested that ILP restored the estrous cycle in rats with PCOS as well as lowered relative ovarian weight and body weight, in comparison to normal. Rats with PCOS showed improvement in ovarian structure and fibrosis when given ILP. ILP decreased the testosterone (T), low-density lipoprotein cholesterol (LDL-C), triglyceride (TG), total cholesterol (TC), luteinizing hormone (LH), homeostasis model assessment-insulin resistance (HOMA-IR), fasting blood glucose (FBG), and insulin (INS) levels and elevated the follicle-stimulating hormone (FSH) and estrogen (E2) levels in PCOS rats. In addition, ILP increased the content of superoxide dismutase (SOD) in serum and the antioxidant enzymes (Prdx3, Sod1, Gsr, Gsta4, Mgst1, Gpx3, Sod2 and Cat) expression levels in the ovaries and decreased the serum expression of malondialdehyde (MDA). In addition, ILP treatment slowed down the process of the fibrosis-associated TGF-ß1/Smad pathway and downregulated α-smooth muscle actin (α-SMA) and connective tissue growth factor (CTGF) levels in PCOS rats ovaries. According to these findings, ILP may be able to treat letrozole-induced PCOS in rats by ameliorating metabolic disturbances, sex hormone levels, oxidative stress, and ovarian fibrosis.

Rhamnocitrin decreases fibrosis of ovarian granulosa cells by regulating the activation of the PPARγ/NF-κB/TGF-ß1/Smad2/3 signaling pathway mediated by Wisp2.

Background: Polycystic ovary syndrome (PCOS) is the most common cause of anovulatory infertility in women. Rhamnocitrin (Rha) has anti-inflammatory and antioxidant actions. The WNT1-inducible-signaling pathway protein 2 (Wisp2) and nuclear factor (NF)-κB are involved in fibrosis in many diseases. We aimed to elucidate the role of Rha in fibrosis of PCOS and the underlying mechanisms. Methods: Dehydroepiandrosterone (DHEA)-incubated ovarian granulosa KGN cells were treated by Rha. Cell proliferation was detected with cell counting kit-8 (CCK-8) and 5-ethynyul-2'-deoxyuridine (EdU) staining. The levels of Wisp2 and transforming growth factor-ß1 (TGF-ß1) in supernatant were measured by enzyme-linked immunosorbent assay (ELISA). We observed α-smooth muscle actin (α-SMA) protein by immunofluorescence (IF). The levels of fibrosis factors were determined using Western blot. We observed p65 nuclear translocation with confocal microscopy. We used Wisp2 overexpression and knockdown in cells treated with DHEA or Rha to validate Wisp2 function. Interaction between Wisp2 and NF-κB, as well as Wisp2 and PPARγ, were assessed by co-immunoprecipitation assay, luciferase reporter assay and chromatin immunoprecipitation (ChIP). Results: The results showed that Rha elevated the reduced proliferation of DHEA-treated cells. In addition, Rha reversed the decreased Wisp2 and the increased TGF-ß1 in supernatant. The proteins CTGF, α-SMA, Collagen I, TGF-ß1, p-Smad2, and p-Smad3 were up-regulated while Wisp2, Sirt1, and PPARγ were down-regulated by DHEA treatment, which were reversed by Rha. Meanwhile, DHEA up-regulated p-IKBa and p-p65 and promoted p65 nuclear translocation, which were inhibited by Rha. These effects of Rha were antagonized by Wisp2 knockdown and were mimicked by Wisp2 overexpression. We confirmed the protein interaction between Wisp2 and NF-κB, along with Wisp2 and PPARγ. Conclusions: Wisp2-mediated PPARγ/NF-κB/TGF-ß1/Smad2/3 signaling contributes to Rha-improved ovarian granulosa cells fibrosis, suggesting Rha as a novel agent for the treatment of PCOS.

Application of New Energy Thermochromic Composite Thermosensitive Materials of Smart Windows in Recent Years.

Thermochromic smart windows technology can intelligently regulate indoor solar radiation by changing indoor light transmittance in response to thermal stimulation, thus reducing energy consumption of the building. In recent years, with the development of new energy-saving materials and the combination with practical technology, energy-saving smart windows technology has received more and more attention from scientific research. Based on the summary of thermochromic smart windows by Yi Long research groups, this review described the applications of thermal responsive organic materials in smart windows, including poly(N-isopropylacrylamide) (PNIPAm) hydrogels, hydroxypropyl cellulose (HPC) hydrogels, ionic liquids and liquid crystals. Besides, the mechanism of various organic materials and the properties of functional materials were also introduced. Finally, opportunities and challenges relating to thermochromic smart windows and prospects for future development are discussed.

[Expression of Versican and Its Related Molecules in Patient with Multiple Myeloma and Its Clinical Significance].

OBJECTIVE: To investigate the expression and clinical significant of VCAN and its related molecules in patients with MM. METHODS: Ficoll density gradient centrifugation method was used to speared the bone marrow mononuclear cell in 25 cases of MM before and after treatment, the relative mRNA expression of VCAN and their related molecules (FAK, FN, MK, and HAS) in bone marrow was detected by real-time quantitative PCR, and their protein expression was determined by Western bolt. RESULTS: The expression of VCAN, FK and FN in the effective group after treatment was significantly lower than that before treatment (P＜0.05), however, the expression of MK and HAS showed no statistically significantly different before and after treatment (P＜0.05). The expression of VCAN of patients in non remission group was significantly higher than that in control group (P＜0.05). The expression of FAK and FN of patients in no remission group was significant increased as compared with the patients in newly diagnosed group (P＜0.05). The relative expression of VCAN mRNA in the patients at 3rd stage was significantly higher than those at the 1st stage (P＜0.05) and control group but showed no significant difference to the patients at 2nd stage (P＜0.05). The expression of VCAN and its related proteins (FAK, MK, FN) showed positively correlation in bone marrow mononuclear cells of MM patients (P＜0.05). The correlation between VCAN and HAS was not statistically significant (r=0.259，P＞0.05). Survival analysis showed that the relative expression of VCAN mRNA was associated with OS (P=0.049) and PFS (P=0.041) in MM patients. CONCLUSION: VCAN and its related molecules are highly expressed in MM patients; VCAN may act as potential biomarker in the development of multiple myeloma.

[Clinical Significance of Platelet Closure Time in Patients with Multiple Myeloma].

OBJECTIVE: To explore the clinical significance of platelet closure time (PCT) in patients with multiple myeloma (MM). METHODS: Peripheral blood samples of 50 newly diagnosed MM patients treated in our hospital from July 2018 to November 2019 and 34 healthy persons underuent physical at the same time were collected. PCT induced by collagen/epinephrine (CEPI) and collagen/adenosinediphosphate (CADP) in peripheral blood were detected by PFA-200，and the clinical data included age, sex, leukocyte count, hemoglobin level, platelet count and level of serum creatinine, cystatin c, blood calcium, ß2-microglobulin (ß2-MG), bone marrow plasma cells, light chain protein, as well as the MM types, ISS stage of patients were collected. RESULTS: The level of PCT in MM patients was significantly higher than that in healthy persons; the level of PCT were significantly increased with the increasing of ISS stage in newly diagnosed MM patients; After chemotherapy with bortezomib/dexamethasone (BD), the level of PCT in 15 patients who were responded to the treatment was significantly lower than those before treatment. CONCLUSION: The platelet closure time is abnormal in MM patients, moreover, relates to the progress of the disease. It has an important clinical significance for the evaluation of diagnostic stage and therapeutic efficacy evaluation of MM patients.

A Gene Selection Method for Microarray Data Based on Binary PSO Encoding Gene-to-Class Sensitivity Information.

Traditional gene selection methods for microarray data mainly considered the features' relevance by evaluating their utility for achieving accurate predication or exploiting data variance and distribution, and the selected genes were usually poorly explicable. To improve the interpretability of the selected genes as well as prediction accuracy, an improved gene selection method based on binary particle swarm optimization (BPSO) and prior information is proposed in this paper. In the proposed method, BPSO encoding gene-to-class sensitivity (GCS) information is used to perform gene selection. The gene-to-class sensitivity information, extracted from the samples by extreme learning machine (ELM), is encoded into the selection process in four aspects: initializing particles, updating the particles, modifying maximum velocity, and adopting mutation operation adaptively. Constrained by the gene-to-class sensitivity information, the new method can select functional gene subsets which are significantly sensitive to the samples' classes. With the few discriminative genes selected by the proposed method, ELM, K-nearest neighbor and support vector machine classifiers achieve much high prediction accuracy on five public microarray data, which in turn verifies the efficiency and effectiveness of the proposed gene selection method.

Preparation and Drug-Delivery Properties of HKUST-1/GO Hybrid.

A hybrid HKUST-1/GO composite was synthesized and its drug loading and drug release abilities were investigated. The adsorption of IBU (ibuprofen) onto the surface of HKUST-1/GO and HKUST-1 composites was compared, and it was found that the addition of GO enhanced both IBU loading and stability. The addition of GO also enhanced the specific surface area. Drug release experiments on IBU loaded HKUST-1 and HKUST-1/GO were conducted, and it was found that drug release of HKUST-1/GO was slower, which can be explained by the hydrogen bonding between GO and IBU. It can be concluded that the addition of GO not only enhances drug loading, but can also achieve a more desirable slow-release of the drug.

[The protective effect of nerve growth factor on PC12 cells to lipopolysaccharide injury].

OBJECTIVE: To investigate the effect of nerve growth factor (NGF) on lipopolysaccharide (LPS) injury and activation of nuclear factor-kappa B in PC12 cells. METHODS: In order to set injury models, the PC12 cells were incubated in different concentration of LPS. Cells were cultured in the culture and were reduced by LPS, and then cells were treated by NGF of various concentrations. The cell viability was determined by methyl thiazolyl tetrazolium (MTT) assay, cellular morphology was observed under inverted microscope and fluorescence microscope, and the content of NF-kappaB was assessed by RT-PCR. RESULTS: (1) The viability of PC12 cell was decreased with concentration of LPS increasing. (2) The cellular morphology change showed that NGF had an ability to reduce LPS injury. (3) The result of RT-PCR showed that the content of NF-kappaB in LPS injury was more than the normal and treated cell, and the treated one was close to the normal one. CONCLUSION: The reports about NGF in brain cells repair after inflammatory are very small. And our study is about that NGF can protect the PC12 cell from LPS injury, and this mechanism possible bears on the activation of NF-kappaB.