Oridonin attenuates liver ischemia-reperfusion injury by suppressing PKM2/NLRP3-mediated macrophage pyroptosis.

BACKGROUND: The NOD-like receptor protein 3 (NLRP3) mediated pyroptosis of macrophages is closely associated with liver ischemia reperfusion injury (IRI). As a covalent inhibitor of NLRP3, Oridonin (Ori), has strong anti-inflammasome effect, but its effect and mechanisms for liver IRI are still unknown. METHODS: Mice and liver macrophages were treated with Ori, respectively. Co-IP and LC-MS/MS analysis of the interaction between PKM2 and NLRP3 in macrophages. Liver damage was detected using H&E staining. Pyroptosis was detected by WB, TEM, and ELISA. RESULTS: Ori ameliorated liver macrophage pyroptosis and liver IRI. Mechanistically, Ori inhibited the interaction between pyruvate kinase M2 isoform (PKM2) and NLRP3 in hypoxia/reoxygenation（H/R）-induced macrophages, while the inhibition of PKM2/NLRP3 reduced liver macrophage pyroptosis and liver IRI. CONCLUSION: Ori exerted protective effects on liver IRI via suppressing PKM2/NLRP3-mediated liver macrophage pyroptosis, which might become a potential therapeutic target in the clinic.

miR-449a ameliorates acute rejection after liver transplantation via targeting procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 in macrophages.

Acute rejection (AR) is an important factor that leads to poor prognosis after liver transplantation (LT). Macrophage M1-polarization is an important mechanism in AR development. MicroRNAs play vital roles in disease regulation; however, their effects on macrophages and AR remain unclear. In this study, rat models of AR were established following LT, and macrophages and peripheral blood mononuclear cells were isolated from rats and humans, respectively. We found miR-449a expression to be significantly reduced in macrophages and peripheral blood mononuclear cells. Overexpression of miR-449a not only inhibited the M1-polarization of macrophages in vitro but also improved the AR of transplant in vivo. The mechanism involved inhibiting the noncanonical nuclear factor-kappaB (NF-κB) pathway. We identified procollagen-lysine1,2-oxoglutarate5-dioxygenase 1 (PLOD1) as a target gene of miR-449a, which could reverse miR-449a's inhibition of macrophage M1-polarization, amelioration of AR, and inhibition of the NF-κB pathway. Overall, miR-449a inhibited the NF-κB pathway in macrophages through PLOD1 and also inhibited the M1-polarization of macrophages, thus attenuating AR after LT. In conclusion, miR-449a and PLOD1 may be new targets for the prevention and mitigation of AR.

HSP110 aggravates ischemia-reperfusion injury after liver transplantation by promoting NF-κB pathway.

BACKGROUND: Ischemia-reperfusion injury (IRI) poses a significant challenge to liver transplantation (LT). The underlying mechanism primarily involves overactivation of the immune system. Heat shock protein 110 (HSP110) functions as a molecular chaperone that helps stabilize protein structures. METHODS: An IRI model was established by performing LT on Sprague-Dawley rats, and HSP110 was silenced using siRNA. Hematoxylin-eosin staining, TUNEL, immunohistochemistry, ELISA and liver enzyme analysis were performed to assess IRI following LT. Western blotting and quantitative reverse transcription-polymerase chain reaction were conducted to investigate the pertinent molecular changes. RESULTS: Our findings revealed a significant increase in the expression of HSP110 at both the mRNA and protein levels in the rat liver following LT (P < 0.05). However, when rats were injected with siRNA-HSP110, IRI subsequent to LT was notably reduced (P < 0.05). Additionally, the levels of liver enzymes and inflammatory chemokines in rat serum were significantly reduced (P < 0.05). Silencing HSP110 with siRNA resulted in a marked decrease in M1-type polarization of Kupffer cells in the liver and downregulated the NF-κB pathway in the liver (P < 0.05). CONCLUSIONS: HSP110 in the liver promotes IRI after LT in rats by activating the NF-κB pathway and inducing M1-type polarization of Kupffer cells. Targeting HSP110 to prevent IRI after LT may represent a promising new approach for the treatment of LT-associated IRI.

Synthesis and antitumor activity evaluation of novel ursolic acid derivatives.

Eleven novel ursolic acid (UA) derivatives were designed and synthesized with modification at positions of C-2, C-3, and C-28 of UA. Their structures were confirmed by MS, (1)H NMR, and elemental analysis. Their in vitro cytotoxicities against various cancer cell lines (HeLa, HepG2, and BGC-823) were evaluated by MTT assay. The results indicated that all compounds could inhibit cell proliferation of HeLa, HepG2, and BGC-823 cells. Among them, compounds I3 and I4 showed more potent cytotoxicity on these three tumor cells than gefitinib (positive control), worthy to be studied further.

[Quantitative Analysis for Levocetirizine Hydrochloride Tablets Based on NIR Spectroscopy].

The aim of this study was to develop a quantitative analytical method to measure the effective components in the left cetirizine hydrochloride tablets using near infrared spectroscopy combining with a partial least square (PLS) analysis model. The method was internal cross-validated to determine the best wavelength range, spectral preprocessing methods and the optimal number of principal components. The concentration of validation set samples was predictable by PLS model. The RMSECV value was 0.276, and the R(2) value was 0.974. Our study suggests that this model can be used for rapid quantitative analysis of left cetirizine hydrochloride tablets from different manufacturers.

[Bidirectional Reflectance Distribution Function of Space-Borne Quartz Volume Diffuser].

Quartz Volume Diffuser(QVD) is used in the observing system of Space-Borne differential optical absorption spectrometer. The precision of observed solar spectrum directly influences the accuracy of the gas retrievals. Therefore the QVD is required for well Lambert feature to ensure the accuracy of full field solar spectrum, and it can provide uniformity source in the observing view of the instrument. Using bidirectional reflectance distribution function(BRDF) measurement instrument, adopting the powder pressboard of F4(polytetrafluoroethylene(PTFE)), QVD's BRDF is measured by choosing the relative measurement method. Four kinds of QVD's BRDF is obtained in the range of 180～880 nm, the observing view of -70°ï½ž+70°. Two kinds of QVD which has a well Lambert feature are selected by analyzing the QVD's BRDF. The diffuse sunlight measured by QVD and F4 is compared, which show that QVD has well scattering properties with regard to solar spectrum and can be selected as the measuring diffuser. That supports for next Ultraviolet irradiation measurement, atomic oxygen erosion measurement and comparison measurement.

[Effects of stereoscopic cultivation on photosynthetic characteristics and growth of Tulipa edulis].

The effect of stereoscopic cultivation on the growth, photosynthetic characteristics and yield of Tulipa edulis was studied to explore the feasibility of stereoscopic cultivation on efficient cultivation of T.edulis. Total leaf area and photosynthetic parameters of T.edulis under stereoscopic cultivation (the upper, middle and the lower layers ) and the control were measured using LI-3100 leaf area meter and LI-6400XT photosynthesis system in the growing peak period of T.edulis.Plant biomass and biomass allocation were also determined.In addition, the bulb regeneration and yield of T.edulis were measured in the harvesting time.The results indicated that in the middle layer of stereoscopic cultivation, leaf biomass proportion was the highest, but total bulb fresh and dry weight and output growth (fresh weight) were the lowest among the treatments.And total bulb fresh weight in the middle of stereoscopic cultivation reduced significantly, by 22.84%, compared with the control.Light intensity in the lower layer of stereoscopic cultivation was moderate, in which T.edulis net photosynthetic rate and water use efficiency were higher than those of the other layers of stereoscopic cultivation, and bulb biomass proportion was the highest in all the treatments.No significant difference was detected in the total bulb fresh weight, dry weight and output growth (fresh weight) between the middle layer of stereoscopic cultivation and the control.In general, there was no significant difference in the growth status of T.edulis between stereoscopic cultivation and the control.Stereoscopic cultivation increased the yield of T.edulis by 161.66% in fresh weight and 141.35% in dry weight compared with the control in the condition of the same land area, respectively.In conclusion, stereoscopic cultivation can improve space utilization, increase the production, and achieve the high density cultivation of T.edulis.

[Spectral Calibration of Space-born Imaging Spectrometers Using Spectrum-Matching Technique].

Spectral calibration of space-born imaging spectrometers based on spectrum-matching technique is presented, which adopts atmospheric absorption lines as the matching lines, and chooses correlation coefficient method as the criteria. In order to simulation the onboard spectral calibration, the spectrum-matching technique is applied on the imaging spectrometers that after the vibration test. The vibration test is able to simulation the launching. The spectral resolution, center wavelength of two-dimensional pixel is determined during onboard spectral calibration. As the calibration results show, the spectral resolution of imaging spectrometers after the vibration test is 0.40 nm, it is the same comparing to the value before the vibration, the wavelength shifts 0.08 nm towards the long wave for the spectral pixels, and the spectral smile is determined for all spatial elements, which shifts towards the short wave direction, with the max smile value is 0.96 nm, the result is similar to that before the vibration. As a result, the spectrum-matching technique is tested and verified.

Study on the Non-Uniformity Calibration of Space-Born Differential Optical Absorption Spectrometer.

Space-borne differential optical absorption spectrometer is a nadir viewing wide field imaging spectrometer, which adopts two-dimensional CCD detector arrays. The pixel response non-uniformity exists in each column of spatial dimension, which will introduce high-frequency instrument-related spectral structures in the measurement data. However, the non-uniformity calibration of space-born imaging spectrometer is difficulty due to two factors: the spectral smile effect and the large field of view. For this reason, a method of non-uniformity calibration is discussed in detail. The result shows that the spectral smile effect and non-uniformity of full FOV image are corrected effectively, and high-frequency instrument-related structures in the measurement data are removed.

[Study on decoction's effect of different processed rhizomes of Cibotium barometz on retinoic acid induced male rats osteoporosis].

This study compared the decoction's HPLC figures of the different processed rhizomes of Cibotium barometz including the raw, the sand-baked, the wined, the steamed and the salted, on the basis of which, with the sand-baked Drynaria fortunei decoction as the positive control group, comparingall groups' decoction, concentration of which was 104.2 g x L(-1), for 4 weeks, by their effects (s-TRAP and total scores of OPG, Ca, P, IL-6, TNF-alpha and IL-1) on retinoic acid induced male rats osteoporosis. The experiment results showed the sand-baked and the wined were better than the steamed, the salted and the raw;in the processing methods' selection, the sand-baked was a better heating method than the steamed and the rice wine was the better excipient than the salt. It provided a reference to explain the processing principle of rhizomes of C. barometz and work mechanism of anti-osteoporosis.