Glycyrrhizae radix et rhizoma processing ameliorates adverse reactions of polygalae radix in zebra fish and rabbit models.

ETHNOPHARMACOLOGICAL RELEVANCE: Polygala tenuifilia Willd (Polygalaceae), a traditional Chinese medicine, has been used for a long time to treat various illnesses with serious adverse reactions. Glycyrrhizae radix et rhizoma processing is generally used to reduce the adverse reactions. AIM OF THE STUDY: The aim of this study was to validate the irritation caused by raw Polygalaceae (RPA), to investigate whether processed Polygalaceae (PGA) was less irritating, and to screen and validate irritant properties of virgaureagenin G (polygala acid, PA), 3,6'-disinapoylsucrose (DSS), Tenuifolia (TEN) and polygalaxanthone III (POL), which had pharmacologically active in Polygalaceae. Zebrafish model, Draize test and High-Performance Liquid Chromatography (HPLC) were utilized to achieve the aim. MATERIALS AND METHODS: Scanning Electron Microscopy (SEM) and optical microscope were used to determine the presence of calcium oxalate needle crystal in RPA and PGA. Zebrafish egg spinning changes and zebrafish embryo behavior were used for irritation validation, irritation comparison and irritant screening. For additional evidence, the Draize test, HE staining of rabbit eyes and ELISA kit were used. Finally, changes in the composition of RPA and PGA were investigated using HPLC. RESULTS: SEM and optical microscopy revealed no calcium oxalate needle crystals in Polygalaceae. RPA, PGA, PA and DSS were able to accelerate the spinning of zebrafish eggs and the movement of embryos, while TEN and POL were not. RPA, PGA, DSS and PA may cause rabbit eyes to become hyperemic and swollen, resulting in damage to the iris, cornea and conjunctiva and increased levels of interleukin-6 (IL-6) and interleukin-10 (IL-10). Comparatively, the effects caused by PGA were less severe than those caused by RPA. In addition, compared to RPA, PGA had lower levels of DSS and PA. CONCLUSIONS: RPA, PGA, DSS, and PA were irritating. However, processing and curing could reduce the irritation by reducing the levels of DSS and PA. DSS and PA could be two potential irritants of Polygalaceae.

The chemometrics analysis and integrated pharmacology approach to decipher the effect and mechanism between raw and processed cistanche tubulosa.

ETHNOPHARMACOLOGICAL RELEVANCE: Cistanche tubulosa (CT) is the dried fleshy stem with scaly leaves of Cistanche tubiflora (Schenk) Wight, which has the effects of tonifying the kidney-yang, benefiting the vital essence and blood, and moisturizing the intestines and laxatives. There are differences in the activity of CT before and after processing, but the mechanism of processing is not clear. AIM OF THE STUDY: The study aimed to compare the strength of action of CT before and after yellow-wine processing in the treatment of constipation and kidney yang deficiency and to identify the active ingredients responsible for the differences in activity before and after yellow-wine processing. MATERIALS AND METHODS: This study established the fingerprints of CT and PCT using HPLC to identify their shared components. Then efficacy of KYDS and FC were carried out to compare the differences between CT and PCT in terms of efficacy. Next, this study established the spectrum-effect relationship between the shared chemical components and the medical effects of CT and PCT using the gray correlation analysis and entropy methods. Ultimately, the activity of the analyzed chemical components was verified using the zebrafish model. RESULTS: CT was more effective than PCT in promoting intestinal peristalsis, regulating gastrointestinal hormone levels, and thus treating FC. PCT was more effective than CT in improving the level of hormone indexes of the hypothalamus-pituitary-target gland axis, replenishing blood, and enhancing immunity. Through the analysis of the spectrum-effect relationship, it was finally found that 5, 6, 12 (tubuloside A), and 13 (isoacteoside) might be more closely related to the activity of tonifying kidney yang, and peaks 9, 10, and 11 (acteoside) are more closely associated with the treatment of constipation, and peaks 3 (salidroside), 4, 1, 2 (geniposidic acid), and 8 (echinacoside) were associated with both kidney yang tonic and treatment of constipation. At the same time, an activity verification experiment showed that echinacoside, geniposidic acid, and salidroside were effective in the treatment of FC and KYDS, while acteoside was very effective in the treatment of FC, and tubuloside A was significant in supplementing the blood, which validated the spectrum-effect relationship analysis. CONCLUSION: This study proved that the raw CT had a better laxative effect, while the yellow-wine processed CT had a better kidney-yang tonic effect; moreover, spectrum-effect relationships were established to analyze the chemical components leading to changes in the activity of CT before and after yellow-wine processing.

Preparation of honokiol-loaded titanium dioxide nanotube drug delivery system and its effect on CAL-27 cells.

Background: Tongue cancer is the most common type of oral cancer, and patients have a poor prognosis and quality of life after conventional surgical treatment. Honokiol (HNK) is a kind of lignan extracted from Chinese herbal medicine Houpu, many domestic and international experiments have demonstrated its anti-tumor effect. Titanium dioxide nanotube (TNTs) is a kind of nanomaterial which can be used as drug carrier. The purpose of this study is to explore the effects of HNK-loaded TNTs delivery system (HNK-TNTs) on anti-tumor. Methods: TNTs were prepared by anodic oxidation method, and HNK was loaded onto TNTs by physical adsorption. The effect of HNK-TNTs on the proliferation, migration and apoptosis of CAL-27 cells were explored by CCK-8 experiment, scratch assay, live and dead staining and cellular immunofluorescence analysis. Results: The material characterization test results showed that we had successfully prepared HNK-TNTs. CCK-8 experiment, scratch assay showed that the proliferation and migration ability of CAL-27 cells were significantly weakened after treatment with HNK-TNTs, and their cell proliferation rates significantly decreased. Live/dead staining, cell immunofluorescence analysis showed that HNK-TNTs could promote CAL-27 cells apoptosis by increasing the expression levels of the apoptosis-related protein Bax and Fas. Conclusion: In this experiment, we had successfully prepared Honokiol-loaded titanium dioxide nanotube drug delivery system (HNK-TNTs) and compared the effects of single drug HNK and HNK-TNTs on the proliferation, apoptosis and migration of tongue cancer CAL-27 cells. This experiment showed that HNK-TNTs had greater anti-proliferative, apoptosis-promoting and migration-inhibiting effects than the HNK as a single drug.

Association between blood selenium levels and gestational diabetes mellitus: A systematic review and meta-analysis.

Introduction: The association between blood (serum or plasma) selenium concentrations and gestational diabetes mellitus (GDM) has been evaluated in some studies. However, the reported findings are debatable, and only case-control and cross-sectional studies were included. Objective: This research aimed to assess the association between blood selenium levels and GDM by analyzing existing literature. To provide a reference for the prevention and treatment of GDM, we included prospective studies which are not included in previous studies to collate more high-quality evidence and better test the etiological hypothesis between blood Se concentrations and GDM. Methods: The PubMed, EMBASE, and Web of Science databases were retrieved for literature up to September 2022, and relevant references were manually searched. Raw data from relevant studies were extracted, and a random effect model was adopted for meta-analysis. The total effects were reported as weighted mean differences. All data were analyzed using Stata 16.0 software. Results: Fourteen studies involving 890 pregnant women with GDM and 1618 healthy pregnant women were incorporated in the meta-analysis. Pregnancies with GDM had significantly lower blood selenium levels than those with normal glucose tolerance (weighted mean difference = -8.11; 95% confidence interval: -12.68 to -3.54, P = 0.001). Subgroup analyses showed that the association between blood selenium levels and GDM was consistent in the residents of Asia and Africa, but not in European. This trend was significant in the second and third trimester subgroups, but not in the first trimester subgroup. Articles published in 2006-2015 also showed this trend, but those published before 2005 and 2016-2019 did not show significant results. This difference was evident in non-prospective studies, but not significant in prospective studies. Studies using the Carpenter and Coustan diagnostic criteria were consistent with this trend, whereas studies using other diagnostic criteria found no differences. In addition, in terms of blood selenium measurement methods, atomic absorption spectrometry showed more significant differences than other methods. In the subgroup analysis based on the sample size of included studies and the quality of the studies, each subgroup showed statistical differences. Conclusion: Lower blood selenium concentrations are associated with GDM as shown in our study. Therefore, supplementing an appropriate amount of selenium may be helpful for GDM prevention and treatment.

Identification of miRNA-mRNA Pairs in Relation to TNF-α/IL-1ß Induced Inflammatory Response in Intervertebral Disc Degeneration.

Objective: The determination of miRNA-mRNA pairs for intervertebral disc degeneration (IVDD) regulated by pro-inflammatory cytokines were investigated. Methods: Two dataset (accession number GSE27494 and GSE41883 from platform GPL1352) of expression profiling was downloaded from Gene Expression Omnibus (GEO). The annulus cells were isolated from annulus fibrosus in patients with degenerative disc disease. The cells were then cultured in a three-dimensional (3D) collagen containing with/without proinflammatory cytokines (tumor necrosis factor alpha (TNF-α) or interleukin beta (IL-1ß)). After being cultured for 14 days, the isolated total RNA was analyzed via microarray, and the expression array data were obtained using BRB-Array Tools followed by analyzing the differentially expressed genes (DEGs) and the prediction of potential miRNA targets of hub genes through online database. Results: Firstly, 52 and 296 DEGs were found in IL-1ß- and TNF-α-induced annulus cells, respectively, of these there had 42 common DEGs (co-DEGs) with 34 increased transcripts and 8 reduced ones. Based on the GO and KEGG software, these co-DEGs were mainly enriched in the response to lipopolysaccharide (LPS) and molecule of bacterial origin, the regulation of receptor ligand activity and signaling receptor activator activity, as well as the following signaling pathways, including TNF signaling pathway, IL-17 signaling pathway, and NF-κB signaling pathway. Top hub genes (CXCL1, CXCL2, CXCL8, IL1Β and PTGS2) regulated by several potential microRNAs were involved in TNF-α/IL-1ß treated annulus cells. Conclusions: Several candidate genes regulated by miRNAs caused by TNF-α/IL-1ß in the annulus cells were found, which will guide diagnosis and treatment for degenerative disc disease.

Exploring the type and strength of nonlinearity in water quality responses to nutrient loading reduction in shallow eutrophic water bodies: Insights from a large number of numerical simulations.

Reducing the load of nutrients is essential to improve water quality while water quality may not respond to the load reduction in a linear way. Despite nonlinear water quality responses being widely mentioned by studies, there is a lack of comprehensive assessment on the extent and type of nonlinear responses considering the seasonal changes. This study aimed to measure the strength of nonlinearity of theoretically possible water quality responses and explore their potential types in shallow eutrophic water bodies. Hereto, we generated 14,710 numerical water body cases that describe the water quality processes using the Environmental Fluid Dynamics Code (EFDC) and applied eight load reduction scenarios on each water body case. Inflows are simplified from Lake Dianchi. The climate conditions consider three cases: Lake Dianchi, Wissahickon Creek, and Famosa Slough. We then developed a nonlinearity strength indicator to quantify the strength and frequency of nonlinear water quality responses. Based on the quantification of nonlinearity, we clustered all the samples of water quality responses using K-Means, an unsupervised Machine Learning algorithm, to find the potential types of nonlinear water quality responses for TN (total nitrogen), TP (total phosphorus), and Chla (chlorophyll a). Results show linear or near-linear response types account for 90%, 69%, and 20% of TN, TP, and Chla samples respectively. TP and Chla could perform more types of nonlinearity. Representative nonlinear water quality responses include disproportional improvement, peak change (disappear, move forwards or afterward), and seasonal deterioration of TN after load reduction. This study would contribute to the current understanding of nonlinear water quality responses to load reduction and provide a basis to study under which conditions the nonlinear responses may emerge.

Cystine supplementation rebalances the redox homeostasis of microenvironment in non-small cell lung cancer cells and reverses their resistance to docetaxel.

Continuous docetaxel (DTX) treatment of non-small cell lung cancer induces development of drug resistance, but the mechanism is poorly understood. In this study we performed metabolomics analysis to characterize the metabolic patterns of sensitive and resistant A549 non-small cell lung cancer cells (A549/DTX cells). We showed that the sensitive and resistant A549 cells exhibited distinct metabolic phenotypes: the resistant cells were characterized by an altered microenvironment of redox homeostasis with reduced glutathione and elevated reactive oxygen species (ROS). DTX induction reprogrammed the metabolic phenotype of the sensitive cells, which acquired a phenotype similar to that of the resistant cells: it reduced cystine influx, inhibited glutathione biosynthesis, increased ROS and decreased glutathione/glutathione disulfide (GSH/GSSG); the genes involved in glutathione biosynthesis were dramatically depressed. Addition of the ROS-inducing agent Rosup (25, 50 µg/mL) significantly increased P-glycoprotein expression and reduced intracellular DTX in the sensitive A549 cells, which ultimately acquired a phenotype similar to that of the resistant cells. Supplementation of cystine (1.0 mM) significantly increased GSH synthesis, rebalanced the redox homeostasis of A549/DTX cells, and reversed DTX-induced upregulation of P-glycoprotein, and it markedly improved the effects of DTX and inhibited the growth of A549/DTX in vitro and in vivo. These results suggest that microenvironmental redox homeostasis plays a key role in the acquired resistance of A549 cancer cells to DTX. The enhancement of GSH synthesis by supplementary cystine is a promising strategy to reverse the resistance of tumor cells and has potential for translation in the clinic.

Volatile Oil of Platycladus Orientalis (L.) Franco Leaves Exerts Strong Anti-inflammatory Effects via Inhibiting the IκB/NF-κB Pathway.

This study was designed to investigate the anti-inflammatory effects of volatile oil of Platycladus orientalis (L.) Franco leaves (VOPF) and the underlying molecular mechanisms by using the non-infectious inflammation rat models and infectious inflammation mouse models. Ear swelling and intraperitoneal capillary permeability in mice, and carrageenan-induced toe swelling and cotton ball-induced granuloma in rats were used to reveal anti-inflammatory effects of VOPF. Moreover, the lipopolysaccharide (LPS)-induced mouse model of acute lung injury was used to explore the anti-inflammatory mechanism of VOPF. The results showed that VOPF could significantly inhibit auricular swelling, intraperitoneal capillary permeability in mice, and reduce granuloma swelling and paw swelling in rats. Furthermore, it significantly alleviated the pathological damage of the lung tissue. In addition, VOPF could reduce the contents of IL-1ß and TNF-α and increase the content of IL-10 in the serum. It had little effect on the expression of p65 but reduced the phosphorylation level of p65 and IκB in NF-κB pathway. In conclusion, VOPF has anti-inflammatory effects and the mechanisms involve the down-regulation of the phosphorylation levels of p65 and IκB and blockage of the NF-κB signaling pathway.

Hyodeoxycholic acid (HDCA) suppresses intestinal epithelial cell proliferation through FXR-PI3K/AKT pathway, accompanied by alteration of bile acids metabolism profiles induced by gut bacteria.

Bile acids (BAs) have been implicated in regulation of intestinal epithelial signaling and function. This study aimed to investigate the effects of hyodeoxycholic acid (HDCA) on intestinal epithelial cell proliferation and explore the underlying mechanisms. IPEC-J2 cells and weaned piglets were treated with HDCA and the contributions of cellular signaling pathways, BAs metabolism profiles and gut bacteria were assessed. In vitro, HDCA suppressed IPEC-J2 proliferation via the BAs receptor FXR but not TGR5. In addition, HDCA inhibited the PI3K/AKT pathway, while knockdown of FXR or constitutive activation of AKT eliminated the inhibitory effects of HDCA, suggesting that FXR-dependent inhibition of PI3K/AKT pathway was involved in HDCA-suppressed IPEC-J2 proliferation. In vivo, dietary HDCA inhibited intestinal expression of proliferative markers and PI3K/AKT pathway in weaned piglets. Meanwhile, HDCA altered the BAs metabolism profiles, with decrease in primary BA and increase in total and secondary BAs in feces, and reduction of conjugated BAs in serum. Furthermore, HDCA increased abundance of the gut bacteria associated with BAs metabolism, and thereby induced BAs profiles alternation, which might indirectly contribute to HDCA-suppressed cell proliferation. Together, HDCA suppressed intestinal epithelial cell proliferation through FXR-PI3K/AKT signaling pathway, accompanied by alteration of BAs metabolism profiles induced by gut bacteria.

cis 9, trans 11, but not trans 10, cis 12 CLA isomer, impairs intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway.

This study aimed to investigate the effects of conjugated linoleic acid (CLA) on intestinal epithelial barrier function and explore the underlying mechanisms. IPEC-J2 cells and mice were treated with different CLA isomers. The intestinal epithelial barrier function determined by transepithelial electrical resistance (TEER), the expression of tight junction proteins, and the involvement of G-protein coupled receptor 120 (GPR120), intracellular calcium ([Ca2+]i) and myosin light chain kinase (MLCK) were assessed. In vitro, c9, t11-CLA, but not t10, c12-CLA isomer, impaired epithelial barrier function in IPEC-J2 by downregulating the expression of tight junction proteins. Meanwhile, c9, t11-CLA isomer enhanced GPR120 expression, while knockdown of GPR120 eliminated the impaired epithelial barrier function induced by c9, t11-CLA isomer. In addition, c9, t11-CLA isomer increased [Ca2+]i and activated the MLCK signaling pathway in a GPR120-dependent manner. However, chelation of [Ca2+]i reversed c9, t11-CLA isomer-induced MLCK activation and the epithelial barrier function impairment of IPEC-J2. Furthermore, inhibition of MLCK totally abolished the impairment of epithelial barrier function induced by c9, t11-CLA. In vivo, dietary supplementation of c9, t11-CLA rather than t10, c12-CLA isomer decreased the expression of intestinal tight junction proteins and GPR120, increased intestinal permeability, and activated the MLCK signaling pathway in mice. Taken together, our findings showed that c9, t11-CLA, but not t10, c12-CLA isomer, impaired intestinal epithelial barrier function in IPEC-J2 cells and mice through activation of GPR120-[Ca2+]i and the MLCK signaling pathway. These data provided new insight into the regulation of the intestinal epithelial barrier by different CLA isomers and more references for CLA application in humans and animals.

Effects of maternal dietary supplementation of phytosterol esters during gestation on muscle development of offspring in mice.

The development of muscle in the embryo, which is crucial for postnatal skeletal muscle growth, has been investigated widely. Much has been learned during the past several decades about the role of maternal nutrition in the outcome of pregnancy. Protein and carbohydrate levels during pregnancy have been shown to be important in the development of offspring, especially muscle development. However, the maternal effects of steroids were still not clear. Phytosterol esters (PEs) are produced by the esterification of phytosterols and fatty acids and have many beneficial functions, such as anti-inflammation and hypolipemic functions. Through the effect of regulation on lipid metabolism, can pregnant mice fed with PEs show any programming effect on the muscle development of offspring? In our study, PEs were supplied to the maternal diet, and changes in maternal lipid metabolism and the development of offspring skeletal muscle were detected. As a result, the amniotic fluid total bile acid (TBA) and total cholesterol (TC) levels were decreased; the growth of offspring was significantly faster than that of the control group until 6 weeks of age. Adult offspring had a higher lean mass index and grip strength. In skeletal muscle, the proportion of myosin heavy chain (MHC) 1 was significantly decreased, while the proportion of MHC 2 b was increased. In conclusion, maternal PEs significantly reduced sterols in the amniotic fluid, while skeletal muscle development was promoted in the offspring.

The Effects of Ginsenosides and Anserine on the Up-Regulation of Renal Aquaporins 1-4 in Hyperuricemic Mice.

Hyperuricemia is a metabolic disease of the kidney that results in decreased uric acid excretion. Here, we aimed to investigate the effects of ginsenosides and anserine on hyperuricemia and the expression of aquaporin (AQP) 1-4, which are indicators of renal excretion. Ginsenosides and anserine were administered separately or together after the establishment of hyperuricemia with adenine in BALB/c mice. Renal function indexes such as serum uric acid, creatinine, and urea nitrogen were measured in each group of mice, and the expression of AQP1-4 in renal tissues was detected. Serum uric acid and urea nitrogen were decreased in the ginsenoside and the anserine +UA groups. Meanwhile, the uric acid excretion and clearance rate were clearly increased in the co-treatment +UA group (p<0.05). Moreover, ginsenosides or anserine ginsenosides or anserine alone and treatment with both increased the expression of AQP1-4; however, the synergistic effects were more significantly enhanced (p<0.01). We provide the first reported evidence that ginsenosides and anserine have synergistic effects on uric acid excretion. The improvement in renal function in hyperuricemic mice after treatment with ginsenosides and anserine may result from up-regulation of AQP1-4 expressions.

Calcium Supplementation Alleviates High-Fat Diet-Induced Estrous Cycle Irregularity and Subfertility Associated with Concomitantly Enhanced Thermogenesis of Brown Adipose Tissue and Browning of White Adipose Tissue.

Obesity has been demonstrated as a disruptor of female fertility. Our previous study showed the antiobesity effects of calcium on HFD-fed male mice. However, the role of calcium in alleviating reproductive dysfunction of HFD-fed female mice remains unclear. Here, we found that HFD led to estrus cycle irregularity (longer cycle duration and shorter estrus period) and subfertility (longer conception time, lower fertility index, and less implantations) in mice. However, the HFD-induced reproductive abnormality was alleviated by calcium supplementation. Additionally, calcium supplementation enhanced activation/thermogenesis of BAT and browning of WAT in HFD-fed mice. Consequently, the abnormality of energy metabolism and glucose homeostasis induced by HFD were improved by calcium supplementation, with elevated metabolic rates and core temperature. In conclusion, these data showed that calcium supplementation alleviated HFD-induced estrous cycle irregularity and subfertility associated with concomitantly enhanced BAT thermogenesis and WAT browning, suggesting the potential application of calcium in improving obesity-related reproductive disorders.

Vitamin D Regulates the Expressions of AQP-1 and AQP-4 in Mice Kidneys.

AIM: Vitamin D plays an important role in water and salt homeostasis. The aim of our study was to investigate the underlying relationship of Vitamin D and Aquaporins (AQP). METHODS: The behaviors of 1α (OH)-ase knockout mice and wild type mice were observed before analysis. The ICR mice were treated with vehicle or paricalcitol, a vitamin D analogue, followed by animals receiving a standard diet and free access to drinking water either with aliskiren (renin blocker; 37.5 mg aliskiren in 100 ml water), or telmisartan (a angiotensin II type I receptor blocker; 40 mg telmisartan in 100 ml water) a week before study. The expressions of AQP-1, AQP-4, and renin in mice kidneys were detected by western bolting, immunohistochemistry, and immunofluorescence. RESULTS: Diuresis and polydipsia were observed in 1α (OH)-ase knockout mice, and a decreased water intake and urine output in ICR mice was observed after paricalcitol treatment. Compared with wild type, the AQP-1 expressions were increased in renal papilla and AQP-4 expressions were decreased in renal proximal tubule of 1α(OH) ase knockout mice. In addition, AQP-1 was decreased in renal papilla and AQP-4 expressions were increased in proximal tubule by suppressing renin activity or supplement of Vitamin D analogue. After injecting renin into the lateral ventricle of the 1α(OH)ase knockout mice, the renin expression level was decreased in the kidney, followed by the decrease of AQP-1 in renal papilla and increase of AQP-4 in proximal tubule. CONCLUSIONS: Overall, Vitamin D and renin inhibitors have synergistic effects in regulating water channels in mice kidneys.

Effect of Hydrocolloids on the Retrogradation of Lotus Seed Starch Undergoing an Autoclaving-Cooling Treatment.

The retrogradation properties of lotus seed starch (LS) blended with the hydrocolloids arabic gum (AG), carrageenan (CG), guar gum (GG), and xanthan (XN) were investigated undergoing an autoclaving-cooling treatment, a model for starch retrogradation acceleration. Compared with LS alone, LS-AG showed the increases in syneresis, tan δ (more solid-like behavior), bound water content and immobile water content, molecular weight, the intensity at 480 cm-1 in Raman spectra and the ratio of absorbance 1047 cm-1 /1022 cm-1 (R1047/1022 ) in FT-IR spectra. The results suggested that the addition of AG tended to promote the starch retrogradation, which was related to the increased molecular migration of free water, interactions of molecular starch chains, and the formation of ordered structures. The addition of CG, GG, or XN significantly decreased the syneresis, tan δ, the intensity at 480 cm-1 , and R1047/1022 values of LS, indicating the prevention of LS retrogradation. The effects of CG and XN on starch retrogradation mainly resulted from competition for water and the increased viscosity, as well as the coating effect on starch. The dominant viscosity of GG was the main factor that influenced starch retrogradation. These results showed not all hydrocolloids would retard starch retrogradation under autoclaving-cooling treatment, for which fine structures altered by different hydrocolloids were the key factors. PRACTICAL APPLICATION: Effects of hydrocolloids on the retrogradation of lotus seed starch were investigated undergoing an autoclaving-cooling treatment. The results will help guide the production and development of starchy foods having desirable properties by specific hydrocolloids during autoclaving-cooling process, especially to control starch retrogradation.

Self-Powered Chemical Sensing Driven by Graphene-Based Photovoltaic Heterojunctions with Chemically Tunable Built-In Potentials.

Ultralow power chemical sensing is essential toward realizing the Internet of Things. However, electrically driven sensors must consume power to generate an electrical readout. Here, a different class of self-powered chemical sensing platform based on unconventional photovoltaic heterojunctions consisting of a top graphene (Gr) layer in contact with underlying photoactive semiconductors including bulk silicon and layered transition metal dichalcogenides is proposed. Owing to the chemically tunable electrochemical potential of Gr, the built-in potential at the junction is effectively modulated by absorbed gas molecules in a predictable manner depending on their redox characteristics. Such ability distinctive from bulk photovoltaic counterparts enables photovoltaic-driven chemical sensing without electric power consumption. Furthermore, it is demonstrated that the hydrogen (H2 ) sensing properties are independent of the light intensity, but sensitive to the gas concentration down to the 1 ppm level at room temperature. These results present an innovative strategy to realize extremely energy-efficient sensors, providing an important advancement for future ubiquitous sensing.

Calcium Supplementation Enhanced Adipogenesis and Improved Glucose Homeostasis Through Activation of Camkii and PI3K/Akt Signaling Pathway in Porcine Bone Marrow Mesenchymal Stem Cells (pBMSCs) and Mice Fed High Fat Diet (HFD).

BACKGROUND/AIMS: It has been implicated that calcium supplementation is involved in reducing body weight/fat and improving glucose homeostasis. However, the underlying mechanisms are still not fully understood. Here, we investigated the effects of calcium supplementation on adipogenesis and glucose homeostasis in porcine bone marrow mesenchymal stem cells (pBMSCs) and high fat diet (HFD)-fed mice and explored the involved signaling pathways. METHODS: In vitro, pBMSCs were treated with 4 mM extracellular calcium ([Ca2+]o) and/or 1 µM nifedipine, 0.1 µM BAPTA-AM, 1 µM KN-93, 50 nM wortmannin for 10 days. The intracellular calcium ([Ca2+]i) levels were measured using Fluo 3-AM by flow cytometry. The adipogenic differentiation of pBMSCs was determined by Oil Red-O staining and triglyceride assay. The expression of marker genes involved in adipogenesis (peroxisome proliferator activated receptor γ (PPARγ) and CCAAT/enhancer binding protein α (C/EBPα)) and glucose uptake (glucose transporter 4 (GLUT4)), as well as the activation of Ca2+/calmodulin-dependent protein kinase II (CaMKII) and PI3K/Akt-FoxO1/AS160 signaling pathways were determined by Western blotting. Glucose uptake and utilization were examined using 2-NBDG assay and glucose content assay, respectively. In vivo, C57BL/6J male mice were fed a HFD (containing 1.2% calcium) without or with 0.6% (w/w) calcium chloride in drinking water for 13 weeks. The adipogenesis, glucose homeostasis and the involvement of CaMKII and PI3K/Akt signaling pathway were also assessed. RESULTS: In vitro, [Ca2+]o stimulated pBMSCs adipogenesis by increasing [Ca2+]i level and activating CaMKII and PI3K/Akt-FoxO1 pathways. In addition, [Ca2+]o promoted glucose uptake/utilization by enhancing AS160 phosphorylation, GLUT4 expression and translocation. However, the stimulating effects of [Ca2+]o on pBMSCs adipogenesis and glucose uptake/utilization were abolished by L-VGCC blocker Nifedipine, [Ca2+]i chelator BAPTA-AM, CaMKII inhibitor KN-93, or PI3K inhibitor Wortmannin. In vivo, calcium supplementation decreased body weight and fat content, increased adipocyte number, and improved glucose homeostasis, with elevated PPARγ and GLUT4 expression and PI3K/Akt activation in iWAT. CONCLUSION: calcium supplementation enhanced adipogenesis and glucose uptake in pBMSCs, which was coincident with the increased adipocyte number and improved glucose homeostasis in HFD-fed mice, and was associated with activation of CaMKII and PI3K/Akt-FoxO1/AS160 pathways. These data provided a broader understanding of the mechanisms underlying calcium-induced body weight/fat loss and glycemic control.

Riligustilide Attenuated Renal Injury by the Blockade of Renin.

BACKGROUND/AIMS: Nephropathy related with renin can be alleviated with ACE-inhibitors or AT1R blockers, whereas they might be ineffective after long-term administration because of a feedback production of enhanced renin. Therefore, it is urgent to develop a new category of anti-nephropathy medicine directly targeting renin. Riligustilide (C20), originally isolated from the Chinese herb Ligusticumporteri, a rhizome, was confirmed effective against many diseases. METHODS: The therapeutic effect of C20 on renal injury and its underlying mechanism were investigated in three different nephrotic models, which were spontaneously hypertension rats (SHR) model, diabetic nephropathy in BTBR ob/ob mice model and 5/6-nephrectomized (5/6NX) rats model. RESULTS: The intensity of kidney fibrosis was extensively decreased in the C20-treated rats compared to the vehicle animals. C20 significantly alleviated renal injury much more in 5/6 NX rats than in vehicle group. The rats in 5/6 NX without administrated C20 developed albuminuria earlier with more severe symptoms. Additionally, our findings showed that C20 down-regulated the renin expression and relocation of CREB-CBP complex in vivo and in vitro. CONCLUSION: C20 plays importantly reno-protective roles most likely through the relocation of CREB-CBP complex.

Phytol stimulates the browning of white adipocytes through the activation of AMP-activated protein kinase (AMPK) α in mice fed high-fat diet.

Stimulating the browning of white adipocytes contributes to the restriction of obesity and related metabolic disorders. This study aimed to investigate the browning effects of phytol on mice inguinal subcutaneous white adipose tissue (iWAT) and explore the underlying mechanisms. Our results demonstrated that phytol administration decreased body weight gain and iWAT index, and stimulated the browning of mice iWAT, with the increased expression of brown adipocyte marker genes (UCP1, PRDM16, PGC1α, PDH, and Cyto C). In addition, phytol treatment activated the AMPKα signaling pathway in mice iWAT. In good agreement with the in vivo findings, the in vitro results showed that 100 µM phytol stimulated brown adipogenic differentiation and formation of brown-like adipocytes in the differentiated 3T3-L1 by increasing the mitochondria content and oxygen consumption, and promoting mRNA and/or protein expression of brown adipocyte markers (UCP1, PRDM16, PGC1α, PDH, Cyto C, Cidea and Elovl3) and beige adipocyte markers (CD137 and TMEM26). Meanwhile, phytol activated the AMPKα signaling pathway in the differentiated 3T3-L1. However, the inhibition of AMPKα with Compound C totally abolished phytol-stimulated brown adipogenic differentiation and formation of brown-like adipocytes. In conclusion, these results showed that phytol stimulated the browning of mice iWAT, which was coincident with the increased formation of brown-like adipocytes in the differentiated 3T3-L1, and appeared to be primarily mediated by the AMPKα signaling pathway. These data provided new insight into the role of phytol in regulating the browning of WAT and suggested the potential application of phytol as a nutritional intervention for the restriction of obesity and related metabolic disorders.

An ICET- A survey on Hypoparathyroidism in Patients with Thalassaemia Major and Intermedia: A preliminary report.

Hypoparathyroidism (HPT) is a rare disease with leading symptoms of hypocalcemia, associated with high serum phosphorus levels and absent or inappropriately low levels of parathyroid hormone (PTH). In patients with thalassemias it is mainly attributed to transfusional iron overload, and suboptimal iron chelation therapy. The main objectives of this survey were to provide data on the prevalence, demographic and clinical features of HPT in thalassemia major (TM) and intermedia (TI) patients living in different countries, and to assess its impact in clinical medical practice. A questionnaire was sent to all Thalassemia Centres participating to the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A) Network.Seventeen centers, treating a total of 3023 TM and 739 TI patients, participated to the study. HPT was reported in 206 (6.8%) TM patients and 33 (4.4%) TI patients. In general, ages ranged from 10.5 to 57 years for the TM group and from 20 to 54 years for the TI group. Of the 206 TM patients and 33 TI patients with HPT, 117 (48.9%) had a serum ferritin level >2.500 ng/ml (54.3% TM and 15.1% TI patients) at the last observation. Hypocalcemia varied in its clinical presentation from an asymptomatic biochemical abnormality to a life-threatening condition, requiring hospitalization. Calcium and vitamin D metabolites are currently the cornerstone of therapy in HPT. In TM patients, HPT was preceded or followed by other endocrine and non-endocrine complications. Growth retardation and hypogonadism were the most common complications (53.3% and 67.4%, respectively). Although endocrine complications were more common in patients with TM, non-transfused or infrequently transfused patients with TI suffered a similar spectrum of complications but at a lower rate than their regularly transfused counterparts.In conclusion, although a large international registry would help to better define the prevalence, comorbidities and best treatment of HPT, through the result of this survey we hope to give a clearer understanding of the burden of this disease and its unmet needs. HPT requires lifelong therapy with vitamin D or metabolites and is often associated with complications and comorbidities.Therefore, it is important for endocrinologists and other physicians, who care for these patients, to be aware of recent advances of this disorder.