Tough, high conductivity pectin polysaccharide-based hydrogel for strain sensing and real-time information transmission.

Hydrogels from natural polymers are eco-friendly, biocompatible and adjustable for manufacturing wearable sensors. However, it is still challenging to prepare natural polymer hydrogel sensors with excellent properties (e.g., high conductivity). Here, we developed a physically cross-linked, highly conductive and multifunctional hydrogel (named PPTP) to address this challenge. The natural renewable pectin-based PPTP hydrogel is synthesized by introducing tannic acid (TA), calcium chloride (CaCl2), and sodium chloride (NaCl) into the pectin/polyvinyl alcohol (PVA) dual network structure. The hydrogel exhibits excellent characteristics, including unique tensile strength (2.6155 MPa), high electrical conductivity (7 S m-1), and high sensitivity (GF = 3.75). It is also recyclable, further enhancing its eco-friendly nature. The PPTP hydrogel can be used for monitoring human joint activities, as flexible electrodes for monitoring electrocardiogram (ECG) signals, and touchable screen pen for electronic skin. Moreover, when combined with Morse code and wireless Bluetooth technology, PPTP hydrogels can be used for underwater and land information encryption, and decryption. Our unique PPTP hydrogel offers promising opportunities for medical monitoring, information transfer, and human-computer interaction.

Negative associations between folate and bacterial vaginosis in the NHANES 2001 to 2004.

BACKGROUND: Bacterial vaginosis (BV) is one of the most common infections among women of reproductive age and accounts for 15-50% of infections globally. The role played by folate in the pathogenesis and progression of BV is poorly understood. The aim of this study was to investigate the association between serum folate, red blood cell (RBC) folate, and BV in American women. METHODS: 1,954 participants from the 2001-2004 National Health and Nutrition Examination Survey (NHANES) program were included in this study. Multiple logistic regression was used to analyze the association between serum folate, RBC folate, and BV, and covariates including race, age, education level, and body mass index were used to construct adjusted models. Stratified analysis was used to explore the stability of the above associations in different populations. RESULTS: In the present cross-sectional study, we found that serum folate and RBC folate were inversely associated with the risk of BV. In the fully adjusted model, the risk of BV was reduced by 35% (OR=0.65, 95% CI: 0.51~0.83, p=0.0007) in the highest serum folate group and 32% (OR=0.68, 95% CI: 0.53~0.87, p=0.0023) in the highest RBC folate group compared to the lowest group. CONCLUSIONS: The results of this study indicated that serum folate and RBC folate were inversely associated with the risk of BV folate supplementation may play an important role in the prevention and management of BV.

Excellent ultraviolet optical limiting properties of Se nanosheets.

Selenium (Se) is located in the fourth period of the periodic table in group VIA (element 34). In this experiment, three different solvents (isopropyl alcohol, N-methyl-2-pyrrolidone, and ethanol) were used to prepare the two-dimensional Se nanosheets, which were manufactured by the liquid phase exfoliation method with a thickness of 3.35-4.64 nm and a transverse scale of several hundred nanometers. The nonlinear absorption properties at 355, 532, and 1064 nm were studied using the open apertureZ-scan technique. Final results showed that Se nanosheets exhibited optical limiting (OL) effect in all three wavebands and three solvents, and had large two-photon absorption coefficients, especially in ultraviolet (UV) waveband. Which proved that Se nanosheets had great potential application as excellent OL materials in UV waveband. Our research broadens the path for the semiconductor field of Se, inspires the application of Se in nonlinear optics field.

The Low Endometrial Expression of Long Non-Coding RNA NORAD Is Associated with Recurrent Pregnancy Losses and Unexplained Infertility.

Objective: Unexplained infertility (UIF) or recurrent pregnancy loss (RPL) affects 10%-15% of couples in their reproductive years and is multifactorial and not completely elucidated. In this study, we attempt to determine the endometrial expression pattern of non-coding RNA activated by DNA damage (NORAD) in women with UIF and RPL, as well as its clinical significance. Methods: The microarray dataset GSE165004 was used to identify differentially expressed RNAs in the endometrial samples between women with RPL and fertile women and between women with UIF and fertile women. A total of 142 women were included in this retrospective analysis, including 32 women with UIF, 48 women with RPL, and 62 fertile women. The relative expression level of NORAD in the endometrial tissues was quantified by qRT-PCR. Results: NORAD stood out as an only overlapped lncRNA among differentially expressed RNAs in the endometrial samples between RPL and fertile women and between UIF and fertile women. It was showed that the endometrial tissues of UIF and RPL both were demonstrated with lower relative expression levels of NORAD (UIF: 2.09 ± 0.68; RPL: 1.98 ± 0.65) than the endometrial tissues of normal fertility (4.32 ± 1.04) (P < 0.001). Pearson correlation analysis demonstrated that the serum level of E2 was negatively correlated with the relative expression level of NORAD in the endometrial tissues of UIF (r = -0.630) and RPL (r = -0.696). Results of ROC curves showed that the endometrial expression of NORAD could be used to differentiate RPL and UIF with an AUC of 0.977 (95% CI: 0.956-0.999) and 0.970 (95% CI: 0.941-0.998), sensitivity of 0.873 and 0.955, and specificity of 0.845 and 0.948, respectively. Conclusion: The findings obtained from the study showed that the low endometrial expression of NORAD was linked to fertility-related problems, such as UIF and RPL.

Progress of Phototherapy Applications in the Treatment of Bone Cancer.

Bone cancer including primary bone cancer and metastatic bone cancer, remains a challenge claiming millions of lives and affecting the life quality of survivors. Conventional treatments of bone cancer include wide surgical resection, radiotherapy, and chemotherapy. However, some bone cancer cells may remain or recur in the local area after resection, some are highly resistant to chemotherapy, and some are insensitive to radiotherapy. Phototherapy (PT) including photodynamic therapy (PDT) and photothermal therapy (PTT), is a clinically approved, minimally invasive, and highly selective treatment, and has been widely reported for cancer therapy. Under the irradiation of light of a specific wavelength, the photosensitizer (PS) in PDT can cause the increase of intracellular ROS and the photothermal agent (PTA) in PTT can induce photothermal conversion, leading to the tumoricidal effects. In this review, the progress of PT applications in the treatment of bone cancer has been outlined and summarized, and some envisioned challenges and future perspectives have been mentioned. This review provides the current state of the art regarding PDT and PTT in bone cancer and inspiration for future studies on PT.

Serum Levels of HCY, MIF, and hs-CRP Correlate with Glycolipid Metabolism in Adults with Never-Medicated First-Episode Schizophrenia.

OBJECTIVE: It has been reported that the prevalence of metabolic syndrome (MS) in multiepisode patients with schizophrenia is 35.3%, which is 2- to 4-fold higher than in the general population. The study is designed to compare the glycolipid metabolism in patients with first-episode schizophrenia (FES) with sex- and age-matched healthy controls to investigate changes in serum levels of homocysteine (Hcy), macrophage migration inhibitory factor (MIF), and high-sensitive C-reactive protein (hs-CRP) and their relationships with the glycolipid metabolism in patients with FES. METHODS: His case-control study included 88 patients diagnosed with FES and 88 sex- and age-matched healthy controls. Patient psychopathology was assessed using the Positive and Negative Syndrome Scale (PANSS), Young Mania Rating Scale (YMRS), and 17-item Hamilton Rating Scale for Depression (HAMD-17). Patients with FES were classified into MS and non-MS groups. RESULTS: There were significant differences in the education level, body mass index (BMI), and waist circumference between the patients with FES and healthy controls (all p > 0.05). The patients with FES had higher levels of FPG and blood glucose at the oral glucose tolerance test (OGTT) (2 h glucose) concomitant with higher proportion of impaired glucose tolerance (IGT) and homeostasis model assessment of insulin resistance (HOMA2-IR) than healthy controls (all p < 0.001). It was revealed that the patients with FES showed higher serum levels of Hcy, MIF, and hs-CRP than healthy controls (all p < 0.001). The serum level of Hcy shared positive correlations with the score of PANSS totals (r = 0.551) and the negative syndrome of the PANSS scale (r = 0.494). The serum levels of MIF and hs-CRP was only positively correlated with the negative syndrome of the PANSS scale (r = 0.320 and r = 0.446). The level of Hcy shared positive correlations with the levels of FPG, 2 h glucose, and HOMA2-IR; the level of MIF was only positively correlated with the level of HOMA2-IR; the level of hs-CRP had a positive correlation with both levels of FPG and 2 h glucose (all p < 0.001). The levels of Hcy, MIF, and hs-CRP all shared positive correlations with the TG level and negative correlations with the HDL-C level (all p < 0.001). There were remarkable differences between the MS and non-MS groups with regard to BMI, waist circumference, negative subscale of the PANSS scale, FPG, TG, and HDL-C (all p < 0.05). Elevated levels of Hcy, MIF, and hs-CRP were detected in the MS group compared to the non-MS group (all p < 0.05). CONCLUSION: These findings suggest that increased concentrations of HCY, MIF, and hs-CRP may contribute to the abnormal glycolipid metabolism in the context of schizophrenia.

Mixtures of Tea and Citrus maxima (pomelo) Alleviate Lipid Deposition in HepG2 Cells Through the AMPK/ACC Signaling Pathway.

Tea and citrus maxima are natural, medicinal homologous plants, typically used for making beverages, which have anticancer, antiobesity, and antioxidation properties. Green tea, yellow tea, and black tea were combined with citrus maxima to obtain green tea and Citrus maxima (GTCM), yellow tea and Citrus maxima (YTCM), and black tea and Citrus maxima (BTCM). The biochemical components of these mixtures were analyzed, and their possible effects and mechanisms on relieving liver lipid deposition were explored. The tea polyphenols, free amino acids, phenolamine ratio, and caffeine were comparable in YTCM and GTCM, being significantly higher than those in BTCM. In addition, the content of esterified catechins, nonesterified catechins, and total catechins in YTCM was significantly higher than those in GTCM and BTCM. All three mixtures of Citrus maxima tea significantly reduced lipid deposition in HepG2 cells, with GTCM and YTCM being slightly more effective than BTCM. Regarding the possible mechanism, Western blot analysis revealed that the three Citrus maxima tea mixtures could activate the AMPK/ACC signaling pathway, upregulate the expression of p-AMPK, p-ACC, and CPT-1 proteins, and downregulate the expression of SREBP1c and fatty acid synthase proteins to inhibit fat synthesis, thereby relieving lipid deposition in liver cells. In conclusion, as a novel and healthy beverage, Citrus maxima tea has the potential to alleviate liver lipid deposition, and further could be responsible for obesity treatment.

Upregulation of Myeloid Zinc Finger 1 in Dorsal Root Ganglion via Regulating Matrix Metalloproteinase-2/9 and Voltage-gated Potassium 1.2 Expression Contributes to Complete Freund's Adjuvant-induced Inflammatory Pain.

Myeloid zinc finger 1 (MZF1) belongs to the Kruppel family of zinc-finger transcription factors. Recent studies have demonstrated that in dorsal root ganglion (DRG) neurons, MZF1 is involved in the development and maintenance of neuropathic pain. However, the role of MZF1 in inflammatory pain still remains unknown. In the present study, the mechanism of MZF1 in chronic inflammatory pain was investigated in rats received an intraplantar injection of complete Freund's adjuvant (CFA). Subsequently, a series of assays including Western blotting, qRT-PCR, immunohistochemistry, and chromatin immunoprecipitation (ChIP) were performed. We found that CFA led to MZF1 upregulation in ipsilateral L4/5 DRGs. Pre- and post-microinjection of MZF1 siRNA into the ipsi-L5 DRG blocked the development of CFA-induced chronic inflammatory pain and alleviated the mechanical allodynia and thermal hyperalgesia in the maintenance phase. CFA also increased MMP-2/9 and Nav1.8 expression but reduced voltage-gated potassium 1.2 (Kv1.2) and Cav1.2 expression in L4/L5 DRGs. Microinjection of MZF1 siRNA into DRG diminished the CFA-induced changes in MMP-2/9 and Kv1.2 expression. However, the expressions of Nav1.8 and Cav1.2 were not changed by the treatment. Double immunofluorescence staining showed that MMP-2/9 and Kv1.2 were co-localized with MZF1 in DRGs. The ChIP-PCR results revealed that MZF1 binds directly to the promoter region of MMP-2/9 gene. Together, the above results imply that upregulation of MZF1 in DRGs might contribute to the development and maintenance of CFA-induced chronic inflammatory pain by regulating MMP-2/9 and Kv1.2 expression. Targeting DRG-localized MZF1 might be a promising therapeutic strategy for the treatment of chronic inflammatory pain in the clinic.

Baicalin Inhibits Coxsackievirus B3 Replication by Reducing Cellular Lipid Synthesis.

Baicalin is a flavonoid extracted from Scutellariae Radix and shows a variety of biological activities as reducing lipids, diminishing inflammation, and inhibiting bacterial infection. However, there is no report of baicalin against CVB3 infection. In this study, we found that baicalin can reduce viral titer in a dose-dependent manner in vitro at a dose with no direct virucidal effect. Moreover, we revealed that baicalin can also improve survival rate, reduce heart weight/body weight ratio, prevent virus replication, and relieve myocardial inflammation in the acute viral myocarditis mouse model induced by CVB3. Then, in order to explore the mechanism of baicalin inhibiting CVB3 replication, we respectively examined the expression of autophagosome marker LC3-II by Western blot, tested the concentration of free fatty acid (FFA) and cholesterol (CHO) by commercial kits, detected the mRNA levels of fatty acid synthase (Fasn) and acetyl coenzyme a carboxylase (ACC) by RT-PCR, and observed the lipid content of cells by fluorescence staining. The results showed that CVB3 infection increased autophagosome formation and lipid content in HeLa cells, but these changes were significantly blocked by baicalin. Finally, in order to confirm that baicalin inhibits viral replication and reduces autophagosome formation by reducing cellular lipids, we added exogenous palmitate to cell culture supernatants to promote intracellular lipid synthesis and found that palmitate did not alter LC3-II and CVB3/VP1 expression in HeLa cells with or without CVB3 infection. Interestingly, palmitate can reverse the inhibitory effect of baicalin on autophagosome formation and viral replication. In conclusion, our results indicated that lipids play an important role in CVB3 replication, and the effect of baicalin against CVB3 was associated with its ability to reduce cellular lipid synthesis to limit autophagosome formation.

Effects of pulsed electromagnetic field therapy on pain, stiffness and physical function in patients with knee osteoarthritis: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: To evaluate the efficacy of classical pulsed electromagnetic field therapy on patients with knee osteoarthritis. METHODS: The databases PubMed, EMBASE, Web of Science and Cochrane Library were searched for relevant studies. Randomized controlled trials comparing classical pulsed electromagnetic field with placebo for patients with knee osteoarthritis were included. Data for primary outcomes, including pain, stiffness and physical function, were extracted. Data from 8 randomized controlled trials involving 421 patients were pooled. RESULTS: Pulsed electromagnetic field therapy had an effect on improving physical function (weighted mean difference; WMD = -5.28, 95% confidence interval; 95% CI -9.45 to -1.11, p = 0.01), but showed no advantage in the reduction of Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) total score (WMD = -7.80, 95% CI -16.08 to 0.47, p = 0.06), WOMAC pain score (WMD = -1.06, 95% CI -2.30 to 0.17, p = 0.09), visual analogue scale pain score (WMD=-0.88, 95% CI -2.06 to 0.31, p = 0.15) or WOMAC stiffness score (WMD = -0.50, 95% CI -1.09 to 0.09, p = 0.1). CONCLUSION: Pulsed electromagnetic field therapy is beneficial for improving physical function despite having no advantage in treating pain and stiffness. Further randomized controlled trials are needed to confirm these findings and determine the optimal parameters and treatment regimen for pulsed electromagnetic field therapy.

CMOS imager non-uniformity response correction-based high-accuracy spot target localization.

High-accuracy spot target detection based on a complementary metal-oxide semiconductor (CMOS) image sensor, such as astronomy magnitude, medicine, and astronomy photometrics, needs accurate pixel response. Because pixels have different silicon structures and read outputting, each pixel has non-uniformity response with specific illumination. The flat-field correction of a CMOS image sensor is crucial before image processing. In this work, a flat-field model and correction method based on spot scale areas of CMOS image sensor pixel response are proposed. Compared with traditional full-plane calibration, this method aims at spot areas to fit most selected normal pixels' mean response curve with different light intensities and exposure times, which can guarantee spot imaging areas with higher accurate pixel response. Finally, the accuracy of this flat-field correction method is evaluated by the influence on spot target extraction accuracy. The experimental results indicate that using this flat-field correction method can decrease the non-uniform variance from 7.34 (LSB/10 bit) to 1.91 (LSB/10 bit) (improved by 74.1%) and reduce the noise effect on spot extraction accuracy, which improves it from 0.3453 pixel to 0.0116 pixel (1σ). The proposed approach solves the problem of non-uniform pixel response and improves imaging SNR for high-accuracy spot target localization.

Ca2+ and CACNA1H mediate targeted suppression of breast cancer brain metastasis by AM RF EMF.

BACKGROUND: Brain metastases are a major cause of death in patients with metastatic breast cancer. While surgical resection and radiation therapy are effective treatment modalities, the majority of patients will succumb from disease progression. We have developed a novel therapy for brain metastases that delivers athermal radiofrequency electromagnetic fields that are amplitude-modulated at breast cancer specific frequencies (BCF). METHODS: 27.12 MHz amplitude-modulated BCF were administered to a patient with a breast cancer brain metastasis by placing a spoon-shaped antenna on the anterior part of the tongue for three one-hour treatments every day. In preclinical models, a BCF dose, equivalent to that delivered to the patient's brain, was administered to animals implanted with either brain metastasis patient derived xenografts (PDXs) or brain-tropic cell lines. We also examined the efficacy of combining radiation therapy with BCF treatment. Additionally, the mechanistic underpinnings associated with cancer inhibition was identified using an agnostic approach. FINDINGS: Animal studies demonstrated a significant decrease in growth and metastases of brain-tropic cell lines. Moreover, BCF treatment of PDXs established from patients with brain metastases showed strong suppression of their growth ability. Importantly, BCF treatment led to significant and durable regression of brain metastasis of a patient with triple negative breast cancer. The tumour inhibitory effect was mediated by Ca2+ influx in cancer cells through CACNA1H T-type voltage-gated calcium channels, which, acting as the cellular antenna for BCF, activated CAMKII/p38 MAPK signalling and inhibited cancer stem cells through suppression of ß-catenin/HMGA2 signalling. Furthermore, BCF treatment downregulated exosomal miR-1246 level, which in turn decreased angiogenesis in brain environment. Therefore, targeted growth inhibition of breast cancer metastases was achieved through CACNA1H. INTERPRETATION: We demonstrate that BCF, as a single agent or in combination with radiation, is a novel treatment approach to the treatment of brain metastases. This paradigm shifting modality warrants further clinical trials for this unmet medical need.

Effect of cimicifuga racemosa on menopausal syndrome caused by LHRH-a in breast cancer.

ETHNOPHARMACOLOGICAL RELEVANCE: Cimicifuga racemose is previously proved effective on nature menopausal syndrome (MPS). However, its clinical value in treating with MPS induced by luteinizing-hormone releasing hormone analogue (LHRH-a) therapy of pre-/peri-menopausal breast cancer patients is still unknown. AIM OF STUDY: This perspective randomised-design study is to investigate the effect and safety of cimicifuga racemosa on MPS induced by LHRH-a in breast cancer (clinical trial registered: NCT03339882). MATERIALS AND METHODS: Breast cancer patients planning for LHRH-a treatment were randomly divided into 2 groups. The control group which was being treated with the standard treatment of LHRH-a. The other group was being treated with Remifemin, the commercialized product of cimicifuga racemose extract, combined with LHRH-a, called Remifemin group. Our main endpoint was Kupperman menopause index (KMI). Hormone levels in peripheral blood and gynecological complications were also evaluated. RESULTS: Totally, 85 patients (42 in Remifemin group and 43 in control group) were enrolled in Zhejiang Cancer Hospital. At the 4th, 8th and 12th week after using LHRH-a, the KMI were all significantly lower in Remifemin group than in control group (P < 0.01), while the hormone levels, including estradiol (E2), follicle-stimulating hormone (FSH) and luteinizing hormone (LH) were similar in the two groups. In addition, the incidence of cervical cyst in Remifemin group was higher than that in control group (P = 0.02), and there was no significant difference in the other gynecological complications, including endometrial thickening, ovarian cyst or uterine fibroid (P > 0.05). CONCLUSIONS: Cimicifuga racemose is effective, oncological safe and reliable for treatment of MPS caused by LHRH-a in breast cancer.

Baicalin increases hair follicle development by increasing canonical Wnt/ß­catenin signaling and activating dermal papillar cells in mice.

Baicalin is a traditional Chinese herbal medicine commonly used for hair loss, the precise molecular mechanism of which is unknown. In the present study, the mechanism of baicalin was investigated via the topical application of baicalin to reconstituted hair follicles on mice dorsa and evaluating the effect on canonical Wnt/ß­catenin signaling in the hair follicles and the activity of dermal papillar cells. The results indicate that baicalin stimulates the expression of Wnt3a, Wnt5a, frizzled 7 and disheveled 2 whilst inhibiting the Axin/casein kinase 1α/adenomatous polyposis coli/glycogen synthase kinase 3ß degradation complex, leading to accumulation of ß­catenin and activation of Wnt/ß­catenin signaling. In addition, baicalin was observed to increase the alkaline phosphatase levels in dermal papillar cells, a process which was dependent on Wnt pathway activation. Given its non­toxicity and ease of topical application, baicalin represents a promising treatment for alopecia and other forms of hair loss. Further studies of baicalin using human hair follicle transplants are warranted in preparation for future clinical use.

[Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study].

OBJECTIVE: To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice. METHODS: Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated. RESULTS: There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P < 0.01). WBC and PLT were elevated most in Group J, Hb and RBC were also increased at the same time (P < 0.05, P < 0. 01). Compared with Group B, RBC increased in Group E, F, G, I, and J (P < 0.01); Hb obviously increased in Group C, E, F, H, I, and J (P<0.01). Compared with Group B and D, the promotion of erythroid hematopoiesis by G-CSF could be elevated in any group contained drug B and L (P < 0.05, P < 0.01). The spleen index of model mice could be significantly improved in Group C, D, and G (P < 0.01). The thymus index of model mice could be significantly improved in Group H (P < 0.05). CONCLUSIONS: The best scheme to treat mice with chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.

Carnosic acid attenuates apoptosis induced by amyloid-ß 1-42 or 1-43 in SH-SY5Y human neuroblastoma cells.

Amyloid-beta (Aß) peptides, Aß 1-42 (Aß42) and Aß43 in particular, cause neurotoxicity and cell death in the brain of Alzheimer's disease (AD) at higher concentrations. Carnosic acid (CA), a phenolic diterpene compound in the labiate herbs rosemary and sage, serves as an activator for neuroprotective and neurotrophic functions in brain cells. We investigated the effect of CA on apoptosis induced by Aß42 or Aß43 in cultured SH-SY5Y human neuroblastoma cells. Treatment of the cells with Aß42 or Aß43 (monomer, 10 µM each) induced apoptosis, which was confirmed by the cleavage of poly-(ADP-ribose) polymerase (PARP) and apoptosis-inducing factor (AIF). Concurrently, the Aß treatment induced the activation of caspase (Casp) cascades including an effector Casp (Casp3) and initiator Casps (Casp4, Casp8 and Casp9). Pretreatment of the cells with CA (10 µM) partially attenuated the apoptosis induced by Aß42 or Aß43. CA pretreatment also reduced the cellular oligomers of Aß42 and Aß43. These results suggest that CA suppressed the activation of Casp cascades by reducing the intracellular oligomerization of exogenous Aß42/43 monomer. The ingestion of an adequate amount of CA may have a potential in the prevention of Aß-mediated diseases, particularly AD.

Treatment of Chemotherapy Related Leukocytopenia by Oral Administration of Multiple Leucogenic Drugs Combined with G-CSF: an Experimental Study / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To evaluate efficacies of three commonly used oral drugs including Berbamine Hydrochloride Tablet (B), Qijiao Shengbai Capsule (Q), and Leucogen Tablet (L) (by single drug, two drugs or three drugs) combined with granulocyte colony-stimulating factor (G-CSF) for treat ment of chemotherapy related leukocytopenia in mice.</p><p><b>METHODS</b>Totally 156 Kunming male mice were divided into the normal control group (A, n=24), the model group (B, n=24), the G-CSF group (C, n =24), the G-CSF+Q group (D, n=12), G-CSF+ B (E, n=12), the G-CSF+L group (F, n=12), the G-CSF + Q + B group (G, n=12), the G-CSF + Q + L group (H, n=12), the G-CSF + L + B group (I, n=12), and the G-CSF + L + Q + B (J, n=12). Mouse models of chemotherapy related leukocytopenia were established by intraperitoneal injection of cyclophosphamide (CTX). A G-CSF group was set up as a positive control. Mice were treated by a single oral drug, a single oral drug combined with G-CSF, and two or three drugs combined with G-CSF respectively, and the death rate calculated. Hemocytes [such as white blood cells (WBC) and its classification, red blood cells (RBC), platelet (PLT), hemoglobin (Hb)] were calculated by hematology analyzer. Mice were anatomized and important organs weighed. Organ indices were calculated.</p><p><b>RESULTS</b>There was no statistical difference in the mortality rate among all groups (P > 0.05). Compared with Group B, WBC was elevated in all other groups (P < 0.01). WBC and PLT were elevated most in Group J, Hb and RBC were also increased at the same time (P < 0.05, P < 0. 01). Compared with Group B, RBC increased in Group E, F, G, I, and J (P < 0.01); Hb obviously increased in Group C, E, F, H, I, and J (P<0.01). Compared with Group B and D, the promotion of erythroid hematopoiesis by G-CSF could be elevated in any group contained drug B and L (P < 0.05, P < 0.01). The spleen index of model mice could be significantly improved in Group C, D, and G (P < 0.01). The thymus index of model mice could be significantly improved in Group H (P < 0.05).</p><p><b>CONCLUSIONS</b>The best scheme to treat mice with chemotherapy related leukopenia or decreased three blood series was to administrate three commonly oral drugs combined with G-CSF. Authors speculated that G-CSF and Q might have a certain effect on CTX induced immune inhibition.</p>

Carnosic acid suppresses the production of amyloid-ß 1-42 and 1-43 by inducing an α-secretase TACE/ADAM17 in U373MG human astrocytoma cells.

Amyloid beta (Aß) peptides are key molecules in the pathogenesis of Alzheimer's disease (AD). The sequential cleavage of amyloid precursor protein (APP) by the ß- and γ-secretases generates Aß peptides; however, the alternate cleavage of APP by the α- and γ-secretases decreases Aß production. We previously reported that carnosic acid (CA), a phenolic diterpene compound found in the labiate herbs rosemary and sage, suppresses Aß (1-40 and 1-42) production by activating α-secretase in cultured SH-SY5Y human neuroblastoma cells (Neurosci. Res. 2013; 75: 94-102). Here, we investigated the effect of CA on the production of Aß peptides (1-40, 1-42 and 1-43) in U373MG human astrocytoma cells. The treatment of cells with CA suppressed Aß40/42/43 release (55-71% decrease at 50µM). CA treatment enhanced the mRNA expressions of an α-secretase TACE (tumor necrosis factor-α-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17); however, the ß-secretase BACE1 (ß-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα release enhanced by CA and partially recovered the CA-suppressed Aß40/42/43 release. These results suggest that CA reduces Aß production, at least partially, by activating TACE in human astroglial cells. The use of CA may have a potential in the prevention of Aß-mediated diseases.

Carnosic acid suppresses the production of amyloid-ß 1-42 by inducing the metalloprotease gene TACE/ADAM17 in SH-SY5Y human neuroblastoma cells.

A hallmark of Alzheimer's disease (AD) is the aggressive appearance of plaques of amyloid beta (Aß) peptides, which result from the sequential cleavage of amyloid precursor protein (APP) by the ß- and γ-secretases. Aß production is evaded by alternate cleavage of APP by the α- and γ-secretases. Carnosic acid (CA) has been proven to activate the transcription factor Nrf2, a main regulator of the antioxidant response. We investigated the effects of CA on the production of Aß 1-42 peptide (Aß42) and on the expressions of the related genes in SH-SY5Y human neuroblastoma cells. The treatment of cells with CA suppressed Aß42 secretion (61% suppression at 30µM). CA treatment enhanced the mRNA expressions of an α-secretase TACE (tumor necrosis factor-α-converting enzyme, also called a disintegrin and metalloproteinase-17, ADAM17) significantly and another α-secretase ADAM10 marginally; however, the ß-secretase BACE1 (ß-site APP-cleaving enzyme-1) was not increased by CA. Knockdown of TACE by siRNA reduced soluble-APPα secretion enhanced by CA and partially recovered the CA-suppressed Aß42 secretion. These results suggest that CA reduces Aß42 production by activating TACE without promoting BACE1 in human neuroblastoma cells. The use of CA may have a potential in the prevention of Aß-mediated diseases, particularly AD.