Schisandrin A alleviates renal fibrosis by inhibiting PKCß and oxidative stress.

BACKGROUND: Renal fibrosis is a common pathway that drives the advancement of numerous kidney maladies towards end-stage kidney disease (ESKD). Suppressing renal fibrosis holds paramount clinical importance in forestalling or retarding the transition of chronic kidney diseases (CKD) to renal failure. Schisandrin A (Sch A) possesses renoprotective effect in acute kidney injury (AKI), but its effects on renal fibrosis and underlying mechanism(s) have not been studied. STUDY DESIGN: Serum biochemical analysis, histological staining, and expression levels of related proteins were used to assess the effect of PKCß knockdown on renal fibrosis progression. Untargeted metabolomics was used to assess the effect of PKCß knockdown on serum metabolites. Unilateral Ureteral Obstruction (UUO) model and TGF-ß induced HK-2 cells and NIH-3T3 cells were used to evaluate the effect of Schisandrin A (Sch A) on renal fibrosis. PKCß overexpressed NIH-3T3 cells were used to verify the possible mechanism of Sch A. RESULTS: PKCß was upregulated in the UUO model. Knockdown of PKCß mitigated the progression of renal fibrosis by ameliorating perturbations in serum metabolites and curbing oxidative stress. Sch A alleviated renal fibrosis by downregulating the expression of PKCß in kidney. Treatment with Sch A significantly attenuated the upregulated proteins levels of FN, COL-I, PKCß, Vimentin and α-SMA in UUO mice. Moreover, Sch A exhibited a beneficial impact on markers associated with oxidative stress, including MDA, SOD, and GSH-Px. Overexpression of PKCß was found to counteract the renoprotective efficacy of Sch A in vitro. CONCLUSION: Sch A alleviates renal fibrosis by inhibiting PKCß and attenuating oxidative stress.

Dihydroartemisinin attenuates ischemia/reperfusion-induced renal tubular senescence by activating autophagy.

Acute kidney injury (AKI) is an important factor for the occurrence and development of CKD. The protective effect of dihydroartemisinin on AKI and and reported mechanism have not been reported. In this study, we used two animal models including ischemia-reperfusion and UUO, as well as a high-glucose-stimulated HK-2 cell model, to evaluate the protective effect of dihydroartemisinin on premature senescence of renal tubular epithelial cells in vitro and in vivo. We demonstrated that dihydroartemisinin improved renal aging and renal injury by activating autophagy. In addition, we found that co-treatment with chloroquine, an autophagy inhibitor, abolished the anti-renal aging effect of dihydroartemisinin in vitro. These findings suggested that activation of autophagy/elimination of senescent cell might be a useful strategy to prevent AKI/UUO induced renal tubular senescence and fibrosis.

Associations between meeting 24-hour movement guidelines and myopia among school-aged children: A cross-sectional study.

BACKGROUND: The Canadian 24-hour movement behavior (24-HMB) guidelines recommend an adequate level of physical activity (PA), a limited amount of screen time (ST), and a sufficient sleep duration (SLP) to promote the healthy development of children. Although the positive effects of adhering to the 24-HMB guidelines have been established for several health parameters, less is known about how adherence to the 24-HMB guidelines relates to the myopia risk (i.e., inability to see distant objects properly). Thus, this study investigated associations between meeting 24-HMB guidelines and myopia risk in school-aged children. METHOD: Using a questionnaire survey, this cross-sectional study was conducted among parents of school-aged children (5-13 years) in China from 15th September to 15th October 2022, with a total of 1423 respondents with complete data for analysis. Parents reported their child's time spent in moderate-to-vigorous-intensity physical activity (MVPA), SLP, and ST. Multiple logistic regression analyses were performed to examine the associations between measures of PA, ST, and SLP alone and in combination, and the occurrence of myopia. RESULTS: A relatively low percentage of the children being included in the current study (4.92%) met all 24-HMB guidelines, while 32.46% had myopia. Girls had a significantly higher risk of myopia compared to boys (OR = 1.3, 1.002 to 1.68, p = 0.049). Children of parents without myopia had a lower risk of myopia (OR = 0.45, 0.34-0.59, p < 0.001). Children who lived in urban areas (OR = 1.83, 95% CI 1.33 to 2.52, p < 0.001) or towns (OR = 1.60, 1.03 to 2.47, p = 0.04) had a significantly higher risk of myopia compared to those living in rural areas. Meeting SLP guidelines (OR = 0.50, 95% CI 0.31 to 0.82, p < 0.01), meeting ST + SLP guidelines (OR = 0.47, 95% CI 0.32-0.69, <0.001), and meeting all three guidelines were associated with significantly lower risk of myopia (OR = 0.40, 95% CI 0.20-0.82, p = 0.01). Meeting more 24-HMB guidelines was associated with a reduced risk of myopia. CONCLUSIONS: Our data suggest that adhering to SLP, ST + SLP, and ST + SLP + PA guidelines is associated with the risk of myopia. Future research investigating dose-response associations, and potential mechanisms, is necessary to achieve a more nuanced understanding of the observed associations.

Structural characterization and anti-inflammatory activity of neutral polysaccharides from American ginseng.

American ginseng, a precious classic herbal medicine, is used extensively in China for life prolongation purpose. This study aimed to elucidate the structure and anti-inflammatory activity of a neutral polysaccharide isolated from American ginseng (AGP-A). Nuclear magnetic resonance in conjunction with gas chromatography-mass spectrometry were used to analyze AGP-A's structure, whereas Raw264.7 cell and zebrafish models were employed to assess its anti-inflammatory activity. According to the results, AGP-A has a molecular weight of 5561 Da and is primarily consisted of glucose. Additionally, linear α-(1 â†’ 4)-glucans with α-D-Glcp-(1 â†’ 6)-α-Glcp-(1→ residues linked to the backbone at C-6 formed the backbone of AGP-A. Furthermore, AGP-A significantly decreased pro-inflammatory cytokines (IL-1ß, IL-6 and TNF-α) in Raw264.7 cell model. AGP-A in zebrafish model significantly lower the massive recruitment of neutrophils to the neuromast of the caudal lateral line. Inflammation may be relieved by the AGP-A component in American ginseng based on these results. In conclusion, our study shows the structural characterization, remarkable anti-inflammatory properties of AGP-A and its potential curative efficacy as a safe, valid natural anti-inflammatory medicine.

Combined effects of planting patterns and mowing time on different organs and soil stoichiometry of Cyperus esculentus in desert oasis transition zone.

There are many different planting methods for crops, however it is very important to improve the distribution ratio of elements in different organs of crops. Therefore, to understand the effect of different planting patterns on crop element balance, we selected Cyperus esculentus continuous cropping (CC) and C. esculentus - wheat rotation cropping (RC). The leaves, tubers, roots, and soil samples were taken at the mowing time (August 1st, on the 81st day after seed sowing; August 24th, on the 105th day after seed sowing; September 16th, on the 128th day after seed sowing). Results showed that CC and RC had significant effects on soil SO42- and Cl-. With the mowing time, the relative abundance of TN (total nitrogen) in tubers showed an increasing trend, the relative richness of TN in roots decreased, and the relative content of TN in leaves showed no change in the trend under the two planting modes. CC significantly increased the TN/TP (total phosphorus) of leaves, roots, and tubers. However, RC significantly increased the AN (available nitrogen)/AP (available phosphorus) of soil. The random forest analysis (RF) showed that abiotic factors contributed the most to TN/TK (total potassium) of roots, followed by TN/TK of tubers and TP/TK of roots. We found that abiotic factors had no significant impact on TP/TK of leaves and TN/TP of tubers. As expected, different planting patterns alter the plant's N (nitrogen)/P (phosphorus)/K (potassium), which in turn may modify N and P conservation strategies.

Root morphological and physiological traits are committed to the phosphorus acquisition of the desert plants in phosphorus-deficient soils.

BACKGROUND: Phosphorus (P) deficiency in desert ecosystems is widespread. Generally, desert species may allocate an enormous proportion of photosynthetic carbon to their root systems to adjust their P-acquisition strategies. However, root P-acquisition strategies of deep-rooted desert species and the coordination response of root traits at different growth stages to differing soil P availability remains unclear. In this study, a two-year pot experiment was performed with four soil P-supply treatments (0, 0.9, 2.8, and 4.7 mg P kg-1 y-1 for the control, low-, intermediate-, and high-P supply, respectively). Root morphological and physiological traits of one- and two-year-old Alhagi sparsifolia seedlings were measured. RESULTS: For two-year-old seedlings, control or low-P supply significantly increased their leaf Mn concentration, coarse and fine roots' specific root length (SRL), specific root surface area (SRSA), and acid phosphatase activity (APase), but SRL and SRSA of one-year-old seedlings were higher under intermediate-P supply treatment. Root morphological traits were closely correlated with root APase activity and leaf Mn concentration. One-year-old seedlings had higher root APase activity, leaf Mn concentration, and root tissue density (RTD), but lower SRL and SRSA. Two-year-old seedlings had higher root APase activity, leaf Mn concentration, SRL and SRSA, but a lower RTD. Root APase activity was significantly positively correlated with the leaf Mn concentration, regardless of coarse or fine roots. Furthermore, root P concentrations of coarse and fine roots were driven by different root traits, with root biomass and carboxylates secretion particularly crucial root traits for the root P-acquisition of one- and two-year-old seedlings. CONCLUSIONS: Variation of root traits at different growth stages are coordinated with root P concentrations, indicating a trade-off between root traits and P-acquisition strategies. Alhagi sparsifolia developed two P-activation strategies, increasing P-mobilizing phosphatase activity and carboxylates secretion, to acclimate P-impoverished in soil. The adaptive variation of root traits at different growth stages and diversified P-activation strategies are conducive to maintaining the desert ecosystem productivity.

Dietary Leucine Improves Fish Intestinal Barrier Function by Increasing Humoral Immunity, Antioxidant Capacity, and Tight Junction.

This study attempted to evaluate the possible impact and mechanism of leucine (Leu) on fish intestinal barrier function. One hundred and five hybrid Pelteobagrus vachelli ♀ × Leiocassis longirostris ♂ catfish were fed with six diets in graded levels of Leu 10.0 (control group), 15.0, 20.0, 25.0, 30.0, 35.0, and 40.0 g/kg diet for 56 days. Results showed that the intestinal activities of LZM, ACP, and AKP and contents of C3, C4, and IgM had positive linear and/or quadratic responses to dietary Leu levels. The mRNA expressions of itnl1, itnl2, c-LZM, g-LZM, and ß-defensin increased linearly and/or quadratically (p < 0.05). The ROS, PC, and MDA contents had a negative linear and/or quadratic response, but GSH content and ASA, AHR, T-SOD, and GR activities had positive quadratic responses to dietary Leu levels (p < 0.05). No significant differences on the CAT and GPX activities were detected among treatments (p > 0.05). Increasing dietary Leu level linearly and/or quadratically increased the mRNA expressions of CuZnSOD, CAT, and GPX1α. The GST mRNA expression decreased linearly while the GCLC and Nrf2 mRNA expressions were not significantly affected by different dietary Leu levels. The Nrf2 protein level quadratically increased, whereas the Keap1 mRNA expression and protein level decreased quadratically (p < 0.05). The translational levels of ZO-1 and occludin increased linearly. No significant differences were indicated in Claudin-2 mRNA expression and protein level. The transcriptional levels of Beclin1, ULK1b, ATG5, ATG7, ATG9a, ATG4b, LC3b, and P62 and translational levels of ULK1, LC3Ⅱ/Ⅰ, and P62 linearly and quadratically decreased. The Beclin1 protein level was quadratically decreased with increasing dietary Leu levels. These results suggested that dietary Leu could improve fish intestinal barrier function by increasing humoral immunity, antioxidative capacities, and tight junction protein levels.

ß-Hydroxybutyric acid upregulated by Suhuang antitussive capsule ameliorates cough variant asthma through GSK3ß/AMPK-Nrf2 signal axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Cough variant asthma (CVA) is a chronic inflammatory disease characterized by cough as the main symptom. Suhuang antitussive capsule (Suhuang), one of traditional Chinese patent medicines, mainly treats CVA clinically. Previous studies have shown that Suhuang significantly improved CVA, post-infectious cough (PIC), sputum obstruction and airway remodeling. However, the effect of Suhuang on ovalbumin-induced (OVA-induced) metabolic abnormalities in CVA is unknown. AIM OF THE STUDY: This study aimed to identify potential metabolites associated with efficacy of Suhuang in the treatment of CVA, and determined how Suhuang regulates metabolites, and differential metabolites reduce inflammation and oxidative stress. MATERIALS AND METHODS: Rats were given 1 mg OVA/100 mg aluminum hydroxide in the 1st and 7th days by intraperitoneal injection and challenged by atomizing inhalation of 1% OVA saline solution after two weeks to establish the CVA model. Rats were intragastrically (i.g.) administrated with Suhuang at 1.4 g/kg and ß-hydroxybutyric acid (ß-HB) were given with different concentrations (87.5 and 175 mg/kg/day) by intraperitoneal injection for 2 weeks. After 26 days, GC-MS-based metabolomic approach was applied to observe metabolic changes and search differential metabolites. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA), histological analysis and quantitative-polymerase chain reaction (Q-PCR) were used to investigate the effects of Suhuang. Then ß-HB on CVA rats, NLRP3 inflammasome and GSK3ß/AMPK/Nrf2 signalling pathway were detected by western blotting. RESULTS: The results showed that Suhuang treatment significantly enhanced the serum level of ß-HB. Interestingly, exposure to exogenous ß-HB was also protective against OVA-induced CVA. ß-HB significantly reduced the number of coughs and lengthened coughs latencies, improved lung injury, reduced the secretion of various cytokines, and directly inhibited the NLRP3 inflammasome. In addition, ß-HB increased the nuclear accumulation of Nrf2 by activating the GSK3ß/AMPK signaling axis, and then inactivating the NF-κB signaling pathway, effectively protecting OVA-induced CVA from oxidative stress and inflammation. CONCLUSIONS: The results of this study shows that ß-HB can reduce inflammation and oxidative stress, the increased production of ß-HB in serum might be the crucial factor for Suhuang to exert its effect in the treatment of CVA.

Vacancy-Modulated of CuS for Highly Antibacterial Efficiency via Photothermal/Photodynamic Synergetic Therapy.

Cu-based nanomaterials have been developed to alleviate the problem of antibiotic resistance due to their superior properties and good biocompatibility. Defects in nanomaterials have a major role in improving photocatalytic performance. Herein, two CuS nanospheres with predominant VCuSCu and VCuSS vacancy (abbreviated as CuS and CuS-T150, respectively) characterized by positron annihilation spectra are synthesized. The combination of experimental and theoretical calculation results demonstrates that CuS-T150 exhibits excellent antibacterial, achieving bactericidal rates of 99.9% against to Escherichia coli (E. coli) under 808 nm laser irradiation. Compared with CuS, the superior antimicrobial activity of CuS-T150 is mainly attributed to its stronger ability to adsorb oxygen molecules, more easily bind with surface of E. coli, and higher photothermal conversion efficiency (PTCE). This work provides a deeper understanding of nanomaterials with vacancy modulated the antibacterial efficiency by synergistic effect of photodynamic and photothermal therapy.

Phosphorous Supplementation Alleviates Drought-Induced Physio-Biochemical Damages in Calligonum mongolicum.

Calligonum mongolicum is a phreatophyte playing an important role in sand dune fixation, but little is known about its responses to drought and P fertilization. In the present study, we performed a pot experiment to investigate the effects of P fertilization under drought or well-watered conditions on multiple morpho-physio-biochemical attributes of C. mongolicum seedlings. Drought stress leads to a higher production of hydrogen peroxide (H2O2) and malondialdehyde (MDA), leading to impaired growth and metabolism. However, C. mongolicum exhibited effective drought tolerance strategies, including a higher accumulation of soluble sugars, starch, soluble protein, proline, and significantly higheractivities of peroxidase (POD) and catalase (CAT) enzymes. P fertilization increased the productivity of drought-stressed seedlings by increasing their growth, assimilative shoots relative water content, photosynthetic pigments, osmolytes accumulation, mineral nutrition, N assimilation, and reduced lipid peroxidation. Our findings suggest the presence of soil high P depletion and C. mongolicum high P requirements during the initial growth stage. Thus, P can be utilized as a fertilizer to enhance the growth and productivity of Calligonum vegetation and to reduce the fragility of the hyper-arid desert of Taklamakan in the context of future climate change.

Multi-Band Power Amplifier Module with Back-Off Efficiency Improvement using Ultra-Compact 3D Vertical Stack Multi-Chip Package for Cellular Handsets.

A highly integrated multi-mode multi-band (MMMB) power amplifier module (PAM) using hybrid bulk complementary metal oxide semiconductor (CMOS), gallium arsenide (GaAs) heterojunction bipolar transistor (HBT), and silicon-on-insulator (SOI) technologies for low band (LB, 824-915 MHz) and high band (HB, 1710-1980 MHz) is proposed. The hybrid MMMB PAM integrates a bulk CMOS controller die, a GaAs HBT power amplifier (PA) die and a SOI switch die on a six-layer laminate. To simultaneously obtain both highly efficient and highly linear characteristics over a wide range of input power levels, a parallel dual-chain PA strategy has been adopted to provide vary bias current and gain for low-power mode (LPM) and high-power mode (HPM) operation. Additionally, a broadband two-section low-pass output matching network design based on the suppression of high-order harmonics is proposed for enhanced efficiency and linearity. In order to achieve further miniaturization, a three-dimensional (3D) die stack multi-chip module (MCM) packaging structure, where the presented CMOS controller die is stacked vertically on the GaAs HBT PA die, is implemented. The measurement results show that the fabricated MMMB PAM achieves 26.1-27 dB of power gains and 38-38.4% of PAEs at an output power (Pout) of 28 dBm in the HPM, and 20.4-20.9 dB of power gains and 12.4-13.8% of PAEs at Pout of 17 dBm in the LPM over LB. For HB, power gains of 24.3-26.7 dB while maintaining PAEs of 38.2-39.9% at Pout of 28 dBm, and power gains of 15.9-17.5 dB while maintaining PAEs of 12.3-12.8% at Pout of 17 dBm are realized in the HPM and LPM, respectively. The fabricated PAM covering five frequency bands and operating at two power modes only occupies a 5 × 3.5 mm2 area. To the best of the authors' knowledge, this work is the first demonstration of a MMMB PAM adopting an ultra-compact 3D vertical stack MCM package with favorable RF performance.

Neurobehavioral mechanisms underlying the effects of physical exercise break on episodic memory during prolonged sitting.

BACKGROUND AND OBJECTIVE: Episodic memory is the ability that enables individuals to recall and re-experience previous events and usually includes information concerning the spatial and temporal context. This study examined the effects of a physical exercise break during a period of prolonged sitting on episodic memory. Furthermore, we aimed to investigate whether alterations of functional connectivity patterns might contribute to the exercise-induced changes in episodic memory. METHODS: Sixty healthy male college students were randomly assigned (1:1 ratio) to a prolonged-sitting group (PS group) or a physical-exercise-break group (PE group). The face-name paired-associate learning task was used to probe episodic memory. During the task, cortical hemodynamics in the prefrontal cortex were recorded using functional near-infrared spectroscopy (fNIRS). Changes in cortical hemodynamics were used to determine functional connectivity using graph-theoretical network analysis. RESULTS: There was no between-group difference in neurobehavioral outcomes at the pretest assessment. During the posttest assessment, compared with the PS group, higher nodal efficiency in the anterior prefrontal cortex (orbitofrontal and frontopolar cortices) was observed during the encoding phase (FDR corrected p values = 0.039), and higher nodal efficiency and degree centrality of orbitofrontal cortex were observed in the retrieval phase in the PE group (FDR corrected p values = 0.035). Moreover, the PE group showed closer temporal correlational interactions between the dorsolateral prefrontal cortex and the anterior prefrontal cortex in the left hemisphere during the episodic memory encoding phase (FDR corrected p values = 0.043), when compared to the PS group. Neither significant between-group difference in accuracy nor correlations between neural and behavioral outcomes were observed after the intervention. CONCLUSION: Our findings suggest that a physical exercise break during a prolonged sitting period has neither a beneficial nor a detrimental effect on behavioral performance concerning episodic memory. However, physical breaks do facilitate functional connectivity patterns of the prefrontal cortex while performing a episodic memory task.

Intercropping of Leguminous and Non-Leguminous Desert Plant Species Does Not Facilitate Phosphorus Mineralization and Plant Nutrition.

More efficient use of soil resources, such as nitrogen (N) and phosphorus (P), can improve plant community resistance and resilience against drought in arid and semi-arid lands. Intercropping of legume and non-legumes can be an effective practice for enhancing P mineralization uptake, and plant nutrient status. However, it remains unclear how intercropping systems using desert plant species impact soil-plant P fractions and how they affect N and water uptake capacity. Alhagi sparsifolia (a legume) and Karelinia caspia (a non-legume) are dominant plant species in the Taklamakan Desert in Xinjiang Province, China. However, there is a lack of knowledge of whether these species, when intercropped, can trigger synergistic processes and mechanisms that drive more efficient use of soil resources. Thus, in a field experiment over two years, we investigated the impact of monoculture and intercropping of these plant species on soil-plant P fractions and soil-plant nutrients. Both plant species' foliar nutrient (N, P, and K) concentrations were higher under monoculture than intercropping (except K in K. caspia). Nucleic acid P was higher in the monoculture plots of A. sparsifolia, consistent with higher soil labile P, while metabolic P was higher in monoculture K. caspia, associated with higher soil moderately labile Pi. However, both species had a higher residual P percentage in the intercropping system. Soils from monoculture and intercropped plots contained similar microbial biomass carbon (MBC), but lower microbial biomass N:microbial biomass phosphorus (MBN:MBP) ratio associated with reduced N-acetylglucosaminidase (NAG) activity in the intercropped soils. This, together with the high MBC:MBN ratio in intercropping and the lack of apparent general effects of intercropping on MBC:MBP, strongly suggest that intercropping improved microbe N- but not P-use efficiency. Interestingly, while EC and SWC were higher in the soil of the K. caspia monoculture plots, EC was significantly lower in the intercropped plots. Plants obtained better foliar nutrition and soil P mineralization in monocultures than in intercropping systems. The possible positive implications of intercropping for reducing soil salinization and improving soil water uptake and microbial N-use efficiency could have advantages in the long term and its utilization should be explored further in future studies.

Suhuang antitussive capsule ameliorates post-infectious cough in mice through AhR-Nrf2 pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Suhuang antitussive capsule (SH capsule), a typical traditional Chinese medicines (TCMs) compound, is widely used for the treatment of post-infectious cough (PIC) in the clinic. Our previous studies have demonstrated that SH capsule possesses significant ameliorative effects on cough variant asthma (CVA), sputum obstruction and airway remodeling. AIM OF THE STUDY: This study is designed to investigate the ameliorative effects and potential mechanisms of SH capsule on PIC in mice. MATERIALS AND METHODS: To establish the PIC model, ICR mice were induced by lipopolysaccharide (LPS) (3 mg/kg) once, followed by cigarettes smoke (CS) exposure for 30 min per day for 30 days. Mice were intragastrically (i.g.) administrated with SH capsule at the doses of 3.5, 7, 14 g/kg each day for 2 weeks since the 24th day. The number of coughs, coughs latencies, enzyme-linked immunosorbent assay (ELISA) and histological analysis were used to investigate the effects of SH capsule on PIC mice. Quantitative-polymerase chain reaction (Q-PCR) and western blotting were conducted to evaluate the levels of mRNA and proteins associated with Aryl hydrocarbon receptor (AhR)-NF-E2-related factor 2 (Nrf2) pathway. Superoxide dismutase (SOD), glutathione (GSH) and total antioxidant capacity (T-AOC) assays were performed to evaluate the oxidative stress. A549 cells were used to investigate the ameliorative effects of SH capsule in vitro. RESULTS: SH capsule effectively diminished the number of coughs and extended coughs latencies in PIC mice. The airway inflammation was alleviated by decreasing the expression levels of inflammatory mediators including tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and interleukin-6 (IL-6). Moreover, SH capsule dose-dependently activated AhR-Nrf2 pathway and induced the nuclear translocation in vitro and in vivo. Besides, SH capsule significantly increased the levels of SOD, GSH and T-AOC in mice. CONCLUSION: Our study demonstrates that SH capsule ameliorates airway inflammation-associated PIC in mice through activating AhR-Nrf2 pathway and consequently alleviating inflammatory responses and oxidative stress.

Photobiomodulation inhibits the activation of neurotoxic microglia and astrocytes by inhibiting Lcn2/JAK2-STAT3 crosstalk after spinal cord injury in male rats.

BACKGROUND: Neurotoxic microglia and astrocytes begin to activate and participate in pathological processes after spinal cord injury (SCI), subsequently causing severe secondary damage and affecting tissue repair. We have previously reported that photobiomodulation (PBM) can promote functional recovery by reducing neuroinflammation after SCI, but little is known about the underlying mechanism. Therefore, we aimed to investigate whether PBM ameliorates neuroinflammation by modulating the activation of microglia and astrocytes after SCI. METHODS: Male Sprague-Dawley rats were randomly divided into three groups: a sham control group, an SCI + vehicle group and an SCI + PBM group. PBM was performed for two consecutive weeks after clip-compression SCI models were established. The activation of neurotoxic microglia and astrocytes, the level of tissue apoptosis, the number of motor neurons and the recovery of motor function were evaluated at different days post-injury (1, 3, 7, 14, and 28 days post-injury, dpi). Lipocalin 2 (Lcn2) and Janus kinase-2 (JAK2)-signal transducer and activator of transcription-3 (STAT3) signaling were regarded as potential targets by which PBM affected neurotoxic microglia and astrocytes. In in vitro experiments, primary microglia and astrocytes were irradiated with PBM and cotreated with cucurbitacin I (a JAK2-STAT3 pathway inhibitor), an adenovirus (shRNA-Lcn2) and recombinant Lcn2 protein. RESULTS: PBM promoted the recovery of motor function, inhibited the activation of neurotoxic microglia and astrocytes, alleviated neuroinflammation and tissue apoptosis, and increased the number of neurons retained after SCI. The upregulation of Lcn2 and the activation of the JAK2-STAT3 pathway after SCI were suppressed by PBM. In vitro experiments also showed that Lcn2 and JAK2-STAT3 were mutually promoted and that PBM interfered with this interaction, inhibiting the activation of microglia and astrocytes. CONCLUSION: Lcn2/JAK2-STAT3 crosstalk is involved in the activation of neurotoxic microglia and astrocytes after SCI, and this process can be suppressed by PBM.

GC-MS Based Metabolomics Reveals the Synergistic Mechanism of Gardeniae Fructus-Forsythiae Fructus Herb Pair in Lipopolysaccharide-Induced Acute Lung Injury Mouse Model.

Compatibility remains among the crucial and significant characteristics of traditional Chinese medicines. The Gardeniae Fructus (FG)-Forsythiae Fructus (FF) herb pair, an epitome of formulations for heat-clearing and detoxification, is extensively used to treat bacterial pneumonia in clinical settings. However, there are few reports on their synergistic effects. This study thus investigated their compatibility by GC-MS based metabolomics using a lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. Differential metabolites were identified by both variable importance in the projection (VIP) > 1 in orthogonal partial least-squares discriminant analysis (OPLS-DA) mode and P < 0.05. Results of biochemistry and histopathology indicated that FG-FF herb pair exerted more promising lung protective effect than its individual decoction against the LPS-induced ALI model. From the metabolomics study, 32 differential metabolites in vehicle vs. model groups, 21 differential metabolites in FF vs. model groups, 21 differential metabolites in FG vs. model groups, and 20 differential metabolites in FG-FF herb pair vs. model groups were found. Among them, the levels of 3-hydroxybutyric acid, alanine, isophthalic acid, and terephthalic acid were restored significantly in the FF group, while silanol and cholesterol were restored significantly in the FG group. For FG-FF treatment, the amount of behenic acid, a metabolite with anti-inflammatory properties, was increased, while palmitic acid, a proinflammatory metabolite, was decreased. Meanwhile, the two biomarkers were restored more significantly than that by FG or FF treatment, which indicated that the synergistic effects by FF coupled with FG might be attributed to restoring fatty acids metabolic pathway.

Transesophageal echocardiography detection of air embolism during endoscopic surgery and validity of hyperbaric oxygen therapy: Case report.

INTRODUCTION: Air embolism has the potential to be serious and fatal. In this paper, we report 3 cases of air embolism associated with endoscopic medical procedures in which the patients were treated with hyperbaric oxygen immediately after diagnosis by transesophageal echocardiography. In addition, we systematically review the risk factors for air embolism, clinical presentation, treatment, and the importance of early hyperbaric oxygen therapy efficacy after recognition of air embolism. PATIENT CONCERNS: We present 3 patients with varying degrees of air embolism during endoscopic procedures, one of which was fatal, with large amounts of gas visible in the right and left heart chambers and pulmonary artery, 1 showing right heart enlargement with increased pulmonary artery pressure and tricuspid regurgitation, and 1 showing only a small amount of gas images in the heart chambers. DIAGNOSES: Based on ETCO2 and transesophageal echocardiography (TEE), diagnoses of air embolism were made. INTERVENTIONS: The patients received symptomatic supportive therapy including CPR, 100% O2 ventilation, cerebral protection, hyperbaric oxygen therapy and rehabilitation. OUTCOMES: Air embolism can causes respiratory, circulatory and neurological dysfunction. After aggressive treatment, one of the 3 patients died, 1 had permanent visual impairment, and 1 recovered completely without comorbidities. CONCLUSIONS: While it is common for small amounts of air/air bubbles to enter the circulatory system during endoscopic procedures, life-threatening air embolism is rare. Air embolism can lead to serious consequences, including respiratory, circulatory, and neurological impairment. Therefore, early recognition of severe air embolism and prompt hyperbaric oxygen therapy are essential to avoid its serious complications.

Human Methylmercury Exposure and Potential Impacts in Central Tibet: Food and Traditional Tibetan Medicine.

Methylmercury presents potent neurotoxicity to humans. Fish consumption is the leading source of human exposure to methylmercury worldwide. However, the exposure source in Tibet remains poorly understood because of the scarcity of observational data on most Tibetan foods, although high mercury levels were recently detected in some traditional Tibetan medicines. Here, the results of field investigations show that the joint consumption of traditional Tibetan medicines (TTMs), fish, and rice constitutes a primary exposure pathway to methylmercury in Tibetans and that the probable daily intake of methylmercury is close to that for many coastal regions. People who are young and high-income may have higher methylmercury exposure levels mainly because of economic development and cultural exchanges among regions. Our analysis indicates that a large proportion of the Tibetan population are likely to face a high methylmercury exposure risk and that mercury-susceptible populations in Tibet should be attentive to consuming TTMs with fish.

Quantitative determination and characterization of polyphenols from Cissus quadrangularis L. and dietary supplements using UHPLC-PDA-MS, LC-QToF and HPTLC.

Stem and leaf of Cissus quadrangularis L. (Vitaceae), indigenous to Asia and Africa, were used for medicinal and dietary purposes with limited information about the plant's phytochemistry. Stem and leaf samples were assessed for the simultaneous determination of polyphenolic compounds (catechin, epicatechin, quercetin-3-O-ß-glucopyranoside, kaempferol-3-O-ß-glucoside, quercetin-3-O-ß-rhamnoside, leachianol F, amurensin A, pallidol, resveratrol, and quadrangularin A), using UHPLC-PDA-MS. The validation data showed that the method is precise, specific, accurate, and linear over the range of 0.5-100 µg/mL. Reversed-phase ultra-high performance liquid chromatography (UHPLC) fingerprints of the crude methanolic stem and leaf extracts of C. quadrangularis were obtained at different wavelengths based on their λmax. Polyphenolics were characterized using both UHPLC-PDA-MS and LC-QToF analysis. From liquid chromatography quadrupole time of flight-electrospray ionization mass spectrometry (LC-QToF) spectra, over 40 components were structurally correlated, and confirmation was based on the fragmentation characteristics and also from the information available in the literature. In addition to the LC-QToF method, a simple, fast HPTLC method was developed as a visual aid for the rapid qualitative analytical tool to help establish the quality assessment of botanical raw materials and dietary supplements claiming to contain Cissus.

Propionate inhibits fat deposition via affecting feed intake and modulating gut microbiota in broilers.

As one of the 3 main short-chain fatty acids, the role of propionate in chicken fat metabolism is largely unknown. In this study, we demonstrated that dietary supplementation of coated sodium propionate (SP) moderately inhibits fat deposition in broiler chickens, as evidenced by the decreased adipocyte mean area (P < 0.01), the lowered triglyceride content in abdominal fat tissue (P < 0.01), and the reduced transcription of several lipogenic genes in liver and abdominal fat tissues (P < 0.05). Surprisingly, the propionate content was not significantly elevated either in serum or in the cecal chyme by SP administration (P > 0.05). However, SP application significantly decreased the average daily feed intake of broilers (P < 0.05). In addition, the composition of the cecal microbial communities was altered, with the ratio of Firmicutes to Bacteroidetes decreasing in particular (P < 0.05). At the genus level, SP application increased the richness of Alistipes, Lactobacillus, and Bifidobacterium, while reduced the abundance of Lachnospiraceae and Helicobacter significantly (P < 0.05). Moreover, in vitro experiments indicated that, although physiological concentrations of propionate (0.01 to 0.1 mmol) upregulated or downregulated the transcription of some fat synthesis-associated genes (P < 0.05), they did not significantly affect the triglyceride accumulation in hepatocytes and adipocytes (P > 0.05). These results suggest that feed supplementation with SP inhibits fat deposition in broilers by reducing feed and caloric intake, but not via direct regulation on hepatic fat synthesis or adipocytic fat deposition. Alteration in the relative populations of the gut microflora suggests that SP may have gut health implications.