Remodeling of white adipose tissue microenvironment against obesity by phytochemicals.

Obesity is a kind of chronic disease due to a long-term imbalance between energy intake and expenditure. In recent years, the number of obese people around the world has soared, and obesity problem should not be underestimated. Obesity is characterized by changes in the adipose microenvironment, mainly manifested as hypertrophy, chronic inflammatory status, hypoxia, and fibrosis, thus contributing to the pathological changes of other tissues. A plethora of phytochemicals have been found to improve adipose microenvironment, thus prevent and resist obesity, providing a new research direction for the treatment of obesity and related diseases. This paper discusses remodeling of the adipose tissue microenvironment as a therapeutic avenue and reviews the progress of phytochemicals in fighting obesity by improving the adipose microenvironment.

Trend in Research on Characterization, Environmental Impacts and Treatment of Oily Sludge: A Systematic Review.

Oily sludge is a hazardous material generated from the petroleum industry that has attracted increasing research interest. Although several review articles have dealt with specific subtopics focusing on the treatment of oily sludge based on selected references, no attempt has been made to demonstrate the research trend of oily sludge comprehensively and quantitatively. This study conducted a systematic review to analyze and evaluate all oily sludge-related journal articles retrieved from the Web of Science database. The results show that an increase in oily sludge-related research did not take place until recent years and the distribution of the researchers is geographically out of balance. Most oily sludge-related articles focused on treatment for harmfulness reduction or valorization with limited coverage of formation, characterization, and environmental impact assessment of oily sludge. Pyrolytic treatment has attracted increasing research attention in recent years. So far, the research findings have been largely based on laboratory-scale experiments with insufficient consideration of the cost-effectiveness of the proposed treatment methods. Although many methods have been proposed, few alone could satisfactorily achieve cost-effective treatment goals. To enable sustainable management of oily sludge on a global scale, efforts need to be made to fund more research projects, especially in the major oil-producing countries. Pilot-scale experiments using readily available and affordable materials should be encouraged for practical purposes. This will allow a sensible cost-benefit analysis of a proposed method/procedure for oily sludge treatment. To improve the treatment performance, combined methods are more desirable. To inform the smart selection of methods for the treatment of different oily sludge types, it is suggested to develop universally accepted evaluation systems for characterization and environmental risk of oily sludge.

Midazolam increases cisplatin-sensitivity in non-small cell lung cancer (NSCLC) via the miR-194-5p/HOOK3 axis.

BACKGROUNDS: As previously reported, midazolam anesthesia exerts tumor-suppressing effects in non-small cell lung cancer (NSCLC), but the regulating effects of this drug on cisplatin-resistance in NSCLC have not been studied. Thus, we designed this study to investigate this issue and preliminarily delineate the potential molecular mechanisms. METHODS: We performed MTT assay and trypan blue staining assay to measure cell proliferation and viability. Cell apoptosis was examined by FCM. qRT-PCR and immunoblotting were performed to determine the expression levels of genes. The targeting sites between genes were predicted by bioinformatics analysis and were validated by dual-luciferase reporter gene system assay. Mice tumor-bearing models were established and the tumorigenesis was evaluated by measuring tumor weight and volume. Immunohistochemistry (IHC) was used to examine the pro-proliferative Ki67 protein expressions in mice tumor tissues. RESULTS: The cisplatin-resistant NSCLC (CR-NSCLC) cells were treated with high-dose cisplatin (50 µg/ml) and low-dose midazolam (10 µg/ml), and the results showed that midazolam suppressed cell proliferation and viability, and promoted cell apoptosis in cisplatin-treated CR-NSCLC cells. In addition, midazolam enhanced cisplatin-sensitivity in CR-NSCLC cell via modulating the miR-194-5p/hook microtubule-tethering protein 3 (HOOK3) axis. Specifically, midazolam upregulated miR-194-5p, but downregulated HOOK3 in the CR-NSCLC cells, and further results validated that miR-194-5p bound to the 3' untranslated region (3'UTR) of HOOK3 mRNA for its inhibition. Also, midazolam downregulated HOOK3 in CR-NSCLC cells by upregulating miR-194-5p. Functional experiments validated that both miR-194-5p downregulation and HOOK3 upregulation abrogated the promoting effects of midazolam on cisplatin-sensitivity in CR-NSCLC cells. CONCLUSIONS: Taken together, this study found that midazolam anesthesia reduced cisplatin-resistance in CR-NSCLC cells by regulating the miR-194-5p/HOOK3 axis, implying that midazolam could be used as adjuvant drug for NSCLC treatment in clinical practices.

Activation of PI3K-Akt through taurine is critical for propofol to protect rat cardiomyocytes from doxorubicin-induced toxicity.

Myocardial toxicity is one of the major side effects of many chemotherapeutics. It has been shown that propofol can ameliorate the cardiotoxicity of chemotherapeutic agents. In this study, we intend to investigate the role of the PI3K-Akt-Bad signaling pathway in propofol relief of doxorubicin-induced oxidative stress and apoptosis in rat cardiomyocytes. Cultured neonatal rat cardiomyocytes were treated with vehicle, doxorubicin, propofol, or propofol plus doxorubicin in the presence or absence of the PI3K inhibitor LY294002. Cells were harvested 20 h post-exposure to doxorubicin followed by analysis of their cellular taurine content, oxidative/nitrative stresses, and cellular apoptosis. The activation of the PI3K-Akt pathway was analyzed by immunoblotting. FACS, TUNEL, and LDH assays showed that the viability of cardiomyocytes was markedly reduced by doxorubicin, but was improved by propofol. Doxorubicin treatment significantly elevated cellular reactive oxygen and nitrogen contents while lowering the levels of taurine, Akt, and phosphorylated Akt and Bad. The abovementioned doxorubicin-induced changes were reversed by propofol. The protective effects of propofol were abrogated by simultaneous treatment with LY294002. In conclusion, the PI3K-Akt-Bad pathway plays a critical role in conferring the protective effects of propofol against myocardial toxicity from doxorubicin.

Propofol-induced protection of SH-SY5Y cells against hydrogen peroxide is associated with the HO-1 via the ERK pathway.

Propofol (2, 6-diisopropylphenol), is an anesthetic and routinely used for the humans sedation during surgery. The potent inducers of phase II detoxifying and antioxidant stress responsive to propofol were investigated. First, a dose of 25-100 µM propofol showed no significant cytotoxicity on SH-SY5Y cells and pre-treatment of SH-SY5Y cells with propofol (25-100 µM) for 8h prevented cell death and maintained cell integrity following exposure to 1 mM hydrogen peroxide by MTT assays. Then, an increase in the generation of ROS following hydrogen peroxide treatment was significantly attenuated by 8 h pre-treatment with propofol. Additionally, the potential roles of ERK, p 38 MAPK and JNK in the regulation of propofol-induced endogenous HO-1 expression in SH-SY5Y cells were estimated by Western blotting assays. Results showed that propofol significantly increased the phosphorylation levels of ERK, p 38 MAPK and JNK and antioxidant stress responsive to propofol was attenuated by the inhibition of ERK signaling biochemical inhibitors. These results suggest that the ERK pathway plays an important role in the regulation of propofol-mediated antioxidant effects in SH-SY5Y cells.

Effective mechanical properties of frozen hydrogel with ice inclusions.

Hydrogel exhibits attractive mechanical properties that can be regulated to be extremely tough, strong and resilient, adhesive and fatigue-resistant, thus enabling diverse applications ranging from tissue engineering scaffolds, flexible devices, to soft machines. As a liquid-filled porous material composed of polymer networks and water, the hydrogel freezes at subzero temperatures into a new material composed of polymer matrix and ice inclusions: the frozen hydrogel displays dramatically altered mechanical properties, which can significantly affect its safety and reliability in practical applications. In this study, based upon the theory of homogenization, we predicted the effective mechanical properties (e.g., Young's modulus, shear modulus, bulk modulus and Poisson ratio) of a frozen hydrogel with periodically distributed longitudinal ice inclusions. We firstly estimated its longitudinal Young's modulus, longitudinal Poisson ratio and plane strain bulk modulus using the self-consistent method, and then its longitudinal and transverse shear modulus using the generalized self-consistent method; further, the results were employed to calculate its transverse Young's modulus and transverse Poisson ratio. We validated the theoretical predictions against both finite element (FE) simulation and experimental measurement results, with good agreement achieved. We found that the estimated transverse Poisson ratio ranges from 0.3 to 0.53 and, at low volume fraction of ice inclusions, exhibits a value larger than 0.5 that exceeds the Poisson ratios of both the polymer matrix and the ice inclusion (typically 0.33-0.35). Compared with other homogenization methods (e.g., the rule of mixtures, the Halpin-Tsai equations, and the Mori-Tanaka method), the present approach is more accurate in predicting the effective mechanical properties (in particular, the transverse Poisson ratio) of frozen hydrogel. Our study provides theoretical support for the practical applications of frozen liquid-saturated porous materials such as hydrogel.

Critical size of kidney stone through ureter: A mechanical analysis.

Blockage of ureter caused by kidney stone, accompanied by severe pain/infections, is a high incidence urinary tract disease that has received extensive attention. Currently, in clinics, a kidney stone with diameter less than ∼5 mm is considered capable of passing through ureter. However, this critical size (∼5 mm) is empirically based, lacking quantitative analysis. In this study, we proposed a stone-ureter interaction model to quantificationally estimate the critical size of kidney stone passing through ureter. We revealed that the critical size of kidney stone is related to ureter size, about 11%-22% larger than the inner diameter of ureter. Further, based upon the Winkler elastic foundation beam model, we developed a simplified stone-ureter interaction model to evaluate how this critical size is dependent upon the stiffness of ureter and the surface roughness of kidney stone. The proposed model may help urologists improve the accuracy of personalized diagnosis and treatment.

Icariside II enhances Nrf2 nuclear translocation to upregulate phase II detoxifying enzyme expression coupled with the ERK, Akt and JNK signaling pathways.

In the present study, the potent inducers of phase II detoxifying and antioxidant stress responsive to icariside II was investigated. First, a dose of 0-10 µM icariside II showed no significantly cytotoxicity on HepG2 cells by MTT assays and icariside II could enhance cellular GSH levels by ELISA assay. Then, the potential roles of ERK, Akt and JNK in the regulation of icariside II-induced Nrf2-dependent ARE transcriptional activity as well as ARE-mediated endogenous HO-1 and glutathione GST protein expression in HepG2 cells were estimated. Icariside II activated the nuclear translocation of Nrf2 and the up-regulated expression of Nrf2-related antioxidant protein OH-1 and GST were evaluated by Western blotting. Then the phosphorylation levels of ERK1/2, Akt and JNK1/2 were further examined by Western blotting assays. Results showed that icariside II significantly increased the phosphorylation levels of ERK1/2, Akt and JNK1/2. Furthermore, icariside II-induced ARE transcriptional activity was attenuated by the inhibition of ERK, Akt and JNK signaling using biochemical inhibitors. These results suggest that the Nrf2/ARE pathway plays an important role in the regulation of icariside-mediated antioxidant effects in HepG2 cells.

Lidocaine Alleviates Neuropathic Pain and Neuroinflammation by Inhibiting HMGB1 Expression to Mediate MIP-1α/CCR1 Pathway.

High mobility group box 1 (HMGB1) released from sensory nerve tissues can induce neuropathic pain. Whether HMGB1 is implicated in the mechanism underlying the effect of lidocaine in pain management remains to be determined. This study aims to explore the effect of lidocaine in a rat model of spared nerve injury (SNI) and the underlying mechanism. An SNI model was established via nerve ligation. Two weeks after the SNI model was established, rats were intrathecally injected with lidocaine, an HMGB1 antibody (HMG Ab), an MIP-1α antibody (MIP-1α Ab), a CCR1 inhibitor (CCR1-RS) or a CCR5 antagonist (CCR5-Mar). Pain behaviors were assessed before and after model establishment to calculate the number of spontaneous flinches (NSF), paw withdrawal threshold (PWT), paw withdrawal thermal latency (PWL) and sciatic function index (SFI). Cell apoptosis and the inflammatory response in the cerebrospinal fluid (CSF) were detected by TUNEL staining and ELISA. The mRNA and protein expression levels of MIP-1α, CCR1 and CCR5 were determined by RT-PCR and Western blotting. The expression levels of HMGB1, MIP-1α, CCR1 and CCR5 were measured by Western blotting and immunofluorescence. Pain behavior testing in SNI rats showed that SNI rats exhibited an increased NSF and a decreased PWT, PWL and SFI. Cell apoptosis in the spinal dorsal horn and the generation of inflammatory cytokines were enhanced in SNI rats, and the expression levels of HMGB1, MIP-1α, CCR1 and CCR5 were upregulated. HMGB1 cytoplasmic translocation, the coexpression of MIP-1α with NeuN, and the coexpression of CCR1 and CCR5 with OX42 were also observed in SNI rats. Neuropathic pain and neuroinflammation were suppressed by the intrathecal injection of lidocaine, HMG Ab, MIP-1α Ab, CCR1-RS or CCR5-Mar. Lidocaine inhibited the expression levels of HMGB1, MIP-1α, CCR1 and CCR5, and the HMGB1 antibody suppressed the expression of MIP-1α, CCR1 and CCR5. Lidocaine attenuates neuropathic pain and neuroinflammation by inhibiting HMGB1 to regulate the MIP-1α/CCR1/CCR5 pathway. Graphical Abstract.

p38 Mitogen-activated protein kinase is required for electroacupuncture restoration of CD4+/CD8+ homeostasis and cytokine expression in a rodent model of surgical trauma.

Cumulative evidences addressed that electroacupuncture (EA) was favorably effective in the treatment of trauma stress-induced immunodeficiency and physical disorders. However, the salutary effects of EA under operation trauma conditions mediated via p38 MAPK remain unknown. Hence, our study aimed to further investigate the effects of EA on CD4(+)/CD8(+) homeostasis and cytokine expressions, and evaluate the p38 MAPK signaling regulatory mechanism of EA effects.

The complex jujube genome provides insights into fruit tree biology.

The jujube (Ziziphus jujuba Mill.), a member of family Rhamnaceae, is a major dry fruit and a traditional herbal medicine for more than one billion people. Here we present a high-quality sequence for the complex jujube genome, the first genome sequence of Rhamnaceae, using an integrated strategy. The final assembly spans 437.65 Mb (98.6% of the estimated) with 321.45 Mb anchored to the 12 pseudo-chromosomes and contains 32,808 genes. The jujube genome has undergone frequent inter-chromosome fusions and segmental duplications, but no recent whole-genome duplication. Further analyses of the jujube-specific genes and transcriptome data from 15 tissues reveal the molecular mechanisms underlying some specific properties of the jujube. Its high vitamin C content can be attributed to a unique high level expression of genes involved in both biosynthesis and regeneration. Our study provides insights into jujube-specific biology and valuable genomic resources for the improvement of Rhamnaceae plants and other fruit trees.

Structural characterization of natural ideal 6-O-sulfated agarose from red alga Gloiopeltis furcata.

A charge and size uniform polysaccharide GW2M was extracted with cold water from red alga Gloiopeltis furcata and purified by strong anion ion-exchange and gel permeation chromatography. Its chemical structure was identified by methylation, (1)H-(1)H COSY, (1)H-(13)C HMQC and (1)H-(13)C HMBC techniques. The experimental data showed that GW2M was composed of galactose (40.3%), 3,6-anhydro-galactose (34.1%) and sulfate (24.8%) with an average molecular mass of 20.6 kDa. The results proved GW2M was a linear repeating sequence of alternating (1→3)-linked 6-O-sulfated-ß-d-galactose (G6S) and (1→4)-linked 3,6-anhydro-α-l-galactose (A) which made it to be an ideal 6-O-sulfated-agarose. The sequences of serial oligosaccharides prepared by mild acid and reductive acid hydrolysis from GW2M were confirmed using electrospray collision induced dissociation tandem mass spectrometry (ES-CID-MS/MS) technique.