Dietary Polysaccharides Exert Anti-Fatigue Functions via the Gut-Muscle Axis: Advances and Prospectives.

Due to today's fast-paced lifestyle, most people are in a state of sub-health and face "unexplained fatigue", which can seriously affect their health, work efficiency, and quality of life. Fatigue is also a common symptom of several serious diseases such as Parkinson's, Alzheimer's, cancer, etc. However, the contributing mechanisms are not clear, and there are currently no official recommendations for the treatment of fatigue. Some dietary polysaccharides are often used as health care supplements; these have been reported to have specific anti-fatigue effects, with minor side effects and rich pharmacological activities. Dietary polysaccharides can be activated during food processing or during gastrointestinal transit, exerting unique effects. This review aims to comprehensively summarize and evaluate the latest advances in the biological processes of exercise-induced fatigue, to understand dietary polysaccharides and their possible molecular mechanisms in alleviating exercise-induced fatigue, and to systematically elaborate the roles of gut microbiota and the gut-muscle axis in this process. From the perspective of the gut-muscle axis, investigating the relationship between polysaccharides and fatigue will enhance our understanding of fatigue and may lead to a significant breakthrough regarding the molecular mechanism of fatigue. This paper will provide new perspectives for further research into the use of polysaccharides in food science and food nutrition, which could help develop potential anti-fatigue agents and open up novel therapies for sub-health conditions.

A near-infrared and lysosome-targeted BODIPY photosensitizer for photodynamic and photothermal synergistic therapy.

Phototherapy is a promising approach for the treatment of cancers and other diseases. So far, many photosensitizers have been developed for photodynamic therapy (PDT) or photothermal therapy (PTT). However, it remains a challenge to develop a system for synergistic PDT and PTT with specific targeting and real-time fluorescence tracking. Herein, we designed a multifunctional BODIPY derivative, Lyso-BDP, for synergistic PDT and PTT against tumors. Lyso-BDP was composed of three parts: (1) the BODIPY fluorophore was selected as a theranostic core, (2) a morpholine group modified on meso-BODIPY served as a lysosome-targeting unit for enhancing the antitumor effect, and (3) N,N-diethyl-4-vinylaniline was attached to the BODIPY core to extend its wavelength to the near-infrared region. Finally, Lyso-BDP shows near-infrared absorption and emission, photosensitizing activity, lysosomal targeting, and synergistic PDT and PTT effects, and effectively kills cancer cells both in vitro and in vivo. Therefore, our study demonstrates that Lyso-BDP can serve as a promising photosensitizer in the therapy of cancer with potential clinical application prospects.

Association between estimated pulse wave velocity and silent lacunar infarct in a Korean population.

Aims: Previous studies have proposed the estimated pulse wave velocity (ePWV) as a simple and cost-effective measure of arterial stiffness. Since arterial stiffness plays a role in the progression of silent lacunar infarct (SLI), our present work aims to evaluate the association between ePWV and the presence of SLI. Methods: The present work was based on a cross-section study. Our study included 1,011 neurologically healthy Korean participants. The SLI was evaluated using brain magnetic resonance images (MRI). The ePWV was derived from a published equation using age and mean blood pressure (MBP). Logistic regression analyses were performed to investigate the association between ePWV and SLI. The linear relationship and robustness were evaluated using smooth curve fitting and subgroup analyses, respectively. Results: The prevalence of SLI was 11.87%. After fully adjusting for covariates, per 1 m/s increase of ePWV casted 31% additional risk for SLI (P = 0.009). When dividing the ePWV into quartiles, the top quartile had 4.01 times risk compared with the bottom quartile. The increasing trend across the quartiles was statistically significant (P for trend < 0.001). Consistently, smooth curve fitting revealed that the risk of SLI elevated linearly with the increase of ePWV. Finally, subgroup analysis suggested that the association was robust in several sub-populations divided by age, sex, smoking, hypertension, diabetes mellitus (DM), coronary artery occlusive disease (CAOD), hyperlipidemia, and statin medication (all P for interaction > 0.05). Conclusion: The current study revealed an independent and positive association between ePWV and the presence of SLI in a neurologically healthy Korean population.

Polysaccharides from Phellinus linteus: A systematic review of their extractions, purifications, structures and functions.

Phellinus linteus (P. linteus) is a famous Chinese medicine and has a long history in China. In recent years, P. linteus polysaccharides (PLPs) have attracted extensive attention because of their biological activities such as anti-bacteria, anti-aging, anti-oxidation, anti-inflammation, anti-tumor, hepatoprotective effect and hypoglycemic effect. In this review, we systemically summarized the advances in extractions, purifications and structural characterizations of PLPs, and also analyzed their biological functions and molecular mechanisms. Meanwhile, the structure-activity relationships of PLPs are closely related to their anti-oxidation and anti-tumor activities. So far, the applications of PLPs are still very limited, further exploring structure-activity relationships, biological functions and their mechanisms of PLPs will promote to develop functional foods.

HSP90ß promotes osteoclastogenesis by dual-activation of cholesterol synthesis and NF-κB signaling.

Heat shock protein 90ß (Hsp90ß, encoded by Hsp90ab1 gene) is the most abundant proteins in the cells and contributes to variety of biological processes including metabolism, cell growth and neural functions. However, genetic evidences showing Hsp90ß in vivo functions using tissue specific knockout mice are still lacking. Here, we showed that Hsp90ß exerted paralogue-specific role in osteoclastogenesis. Using myeloid-specific Hsp90ab1 knockout mice, we provided the first genetic evidence showing the in vivo function of Hsp90ß. Hsp90ß binds to Ikkß and reduces its ubiquitylation and proteasomal degradation, thus leading to activated NF-κB signaling. Meanwhile, Hsp90ß increases cholesterol biosynthesis by activating Srebp2. Both pathways promote osteoclastogenic genes expression. Genetic deletion of Hsp90ab1 in osteoclast or pharmacological inhibition of Hsp90ß alleviates bone loss in ovariectomy-induced mice. Therefore, Hsp90ß is a promising druggable target for the treatment of osteoporosis.

Laminarin ameliorates alcohol-induced liver damage and its molecular mechanism in mice.

Alcoholic liver disease (ALD) has become a health issue globally. Laminarin, a low molecular weight marine-derived ß-glucan, has been identified with multiple biological activities. In this study, the ameliorative effect on ALD of laminarin isolated from brown algae was investigated. Phenotypic, pathological alterations and biochemical characteristics indicated that laminarin administration (100 mg/kg/day) significantly alleviated liver injury and improved liver function in the alcohol-induced mice. Gene chip results indicated that laminarin treatment caused 52 up-regulated and 13 down-regulated genes in the hepatic tissues of alcohol-induced damage mice, and most of these genes are associated with regulation of oxidative stress (such as CYP450/glutathione-dependent antioxidation), Wnt signaling pathway, retinol metabolism, and cAMP pathway based on GO and KEGG analysis. PPI network analysis indicated that the downstream target genes lied in the hub of the net. Our experiments also confirmed the changed expressions of some target genes. Taken together, these results suggest that laminarin can ameliorate alcohol-induced damage in mice and its molecular mechanism lies in modulating anti-oxidation pathway, WNT pathway, and cAMP pathway, which regulate the expressions of downstream target genes and alleviate alcohol-induced damage. Our study provides new clue to prevent alcohol-induced damage and will be benefit to develop functional foods. PRACTICAL APPLICATIONS: This study verified the positive effect on alcoholic liver disease (ALD) of laminarin, a water-soluble brown algae-derived ß-glucan, linked by ß-(1,3) glycosidic bonds with ß-(1,6) branches. Laminarin significantly alleviated liver injury and improved liver function of ALD mice. Moreover, transcriptomics and bioinformatics analysis further revealed the gene expression patterns, hub targets, and signalings including CYP450/glutathione, Wnt, retinol metabolism, cAMP pathways regulated by laminarin. This research is the first evidence for hepatoprotective effect of laminarin against ALD and its molecular mechanism, which will be advantage to develop functional foods or adjuvant therapy of ALD.

Biological functions of active ingredients in quinoa bran: Advance and prospective.

Quinoa is known to be a rich source of nutrients and bioactive components. Quinoa bran, used mainly as animal feed in processing by-products, is also a potential source of bioactive ingredients being conducive to human health. The importance of nutrition and function of quinoa seed has been discussed in many studies, but the bioactive properties of quinoa bran often are overlooked. This review systemically summarized the progress in bioactive components, extraction, and functional investigations of quinoa bran. It suggests that chemically assisted electronic fractionation could be used to extract albumin from quinoa bran. Ultrasound-assisted extraction method is a very useful method for extracting phenolic acids, triterpene saponins, and flavonoids from quinoa bran. Based on in vitro and in vivo studies for biological activities, quinoa bran extract exhibits a wide range of beneficial properties, including anti-oxidant, anti-diabetes, anti-inflammation, anti-bacterial and anti-cancer functions. However, human experiments and action mechanisms need to investigate. Further exploring quinoa bran will promote its applications in functional foods, pharmaceuticals, and poultry feed in the future.

Near-Infrared Turn-On Fluorescent Probe for Aqueous Fluoride Ion Detection and Cell Imaging.

Fluoride ions are one of the most essential anions in the human body and have been implicated in various pathological and physiological processes. The detection of fluoride ions in aqueous solution, as well as the imaging of fluoride ions in living cells, remains a challenge. We herein report a BODIPY-based fluorescent probe employing a pinacol borate group as the recognition moiety for the detection of fluoride ions in aqueous solutions. This probe shows high selectivity and sensitivity to fluoride ions with a significant near-infrared fluorescence turn-on response. In addition, this probe was successfully employed in fluorescence bioimaging of fluoride ions in the human cervical cancer cell and mouse mammary cancer cell, demonstrating its good cell permeability and stability under physiological conditions.

Creation of cotton mutant library based on linear electron accelerator radiation mutation.

Cotton (Gossypium spp.) is one of the most important cash crops worldwide. At present, new cotton varieties are mainly produced through conventional cross breeding, which is limited by available germplasm. Although the genome of cotton has been fully sequenced, research on the function of specific genes lags behind due to the lack of sufficient genetic material. Therefore, it is very important to create a cotton mutant library to create new, higher-quality varieties and identify genes associated with the regulation of key traits. Traditional mutagenic strategies, such as physical, chemical, and site-directed mutagenesis, are relatively costly, inefficient, and difficult to perform. In this study, we used a radiation mutation method based on linear electron acceleration to mutate cotton variety 'TM-1', for which a whole-genome sequence has previously been performed, to create a high throughput cotton mutant library. Abundant phenotypic variation was observed in the progeny population for three consecutive generations, including cotton fiber color variation, plant dwarfing, significant improvement of yield traits, and increased sensitivity to Verticillium wilt. These results show that radiation mutagenesis is an effective and feasible method to create plant mutant libraries.

Determination of EGFR-overexpressing tumor cells by magnetic gold-decorated graphene oxide nanocomposites based impedance sensor.

This work developed an electrochemical impedance spectroscopy (EIS) sensor for detection of EGFR (epidermal growth factor receptor)-overexpressing tumor cell and preliminary estimation of EGFR expression. Here, EGFR antibodies as the specific antibodies for cancer cells were conjugated on magnetic gold-decorated graphene oxide nanocomposites, which were used to capture the EGFR-overexpressing tumor cells. The magnetically responsive tumor cells were enriched and immobilized on a magnetic glassy carbon electrode (mGCE) surface, leading to increased electron-transfer resistance (Ret) utilized for determination of cells and preliminary evaluation of EGFR expression level. This strategy enables the enrichment, fixation and detection of tumor cells to be accomplished in a facile way. An excellent linearity in the range of 2.0 × 102 - 3.0 × 105 cell mL-1 with the detection limit of 152 cell mL-1 for MDA-MB-231 cells was obtained. Investigation on the expression levels of EGFR on various types of cells was conducted. MDA-MB-231 cells showed a distinctly higher EGFR expression, compared with MHCC97-L and L02 cells, providing the possibility for the EGFR-targeted therapy of the tumors. It is expected that the proposed sensor has the potential to be applied for cancer monitoring.

Phospholipase Dδ and H2S increase the production of NADPH oxidase-dependent H2O2 to respond to osmotic stress-induced stomatal closure in Arabidopsis thaliana.

Osmotic stress is one of the main stresses that seriously affects the survival of plants, destroying normal cell activities, and potentially leading to plant death. Phospholipase D (PLD), a major lipid hydrolase, hydrolyzes membrane phospholipids to produce phosphatidic acid (PA) and responds to many abiotic stresses. Hydrogen sulfide (H2S) emerges as the third gaseous signaling molecule involved in the complex network of signaling events. Hydrogen peroxide (H2O2) plays a crucial role as a signaling molecule in plant development and growth, and responds to various abiotic and biotic stresses. In this study, the functions and the relationship of PLDδ, H2S, and H2O2 in osmotic stress-induced stomatal closure were explored. By using the seedlings of ecotype (WT), PLDδ-deficient mutant (pldδ), l-cysteine desulfhydrase (LCD)-deficient mutant (lcd), and pldδlcd double mutant, atrbohD, and atrbohF mutant as materials, and the stomatal aperture were analyzed. The relative water loss of pldδ, lcd, and pldδlcd was higher than that of WT. Exogenous PA and NaHS could partially alleviate the leaf wilting and yellowing phenotypes of pldδ, lcd, and pldδlcd under osmotic stress, but the mutants could not be restored to the same phenotype as WT. The fluorescence intensity of H2O2 in guard cells of pldδ, lcd, and pldδlcd was lower than that of WT, indicating that PLDδ and LCD were involved in the production of H2O2 in guard cells. Exogenous application of H2O2 to WT, pldδ, lcd, and pldδlcd significantly induced stomatal closure under osmotic stress. Exogenous NaHS induced stomatal closure of WT, but could not induce stomatal closure of atrbohD and atrbohF under osmotic stress. These results suggest that the accumulation of H2O2 was essential to induce stomatal closure under osmotic stress, and PLDδ and LCD acted upstream of H2O2.

A novel LGI1 mutation causing autosomal dominant lateral temporal lobe epilepsy confirmed by a precise knock-in mouse model.

AIMS: This study aimed to explore the pathomechanism of a mutation on the leucine-rich glioma inactivated 1 gene (LGI1) identified in a family having autosomal dominant lateral temporal lobe epilepsy (ADLTE), using a precise knock-in mouse model. METHODS AND RESULTS: A novel LGI1 mutation, c.152A>G; p. Asp51Gly, was identified by whole exome sequencing in a Chinese family with ADLTE. The pathomechanism of the mutation was explored by generating Lgi1D51G knock-in mice that precisely phenocopied the epileptic symptoms of human patients. The Lgi1D51G/D51G mice showed spontaneous recurrent generalized seizures and premature death. The Lgi1D51G/+ mice had partial epilepsy, with half of them displaying epileptiform discharges on electroencephalography. They also showed enhanced sensitivity to the convulsant agent pentylenetetrazole. Mechanistically, the secretion of Lgi1 was impaired in the brain of the D51G knock-in mice and the protein level was drastically reduced. Moreover, the antiepileptic drugs, carbamazepine, oxcarbazepine, and sodium valproate, could prolong the survival time of Lgi1D51G/D51G mice, and oxcarbazepine appeared to be the most effective. CONCLUSIONS: We identified a novel epilepsy-causing mutation of LGI1 in humans. The Lgi1D51G/+ mouse model, precisely phenocopying epileptic symptoms of human patients, could be a useful tool in future studies on the pathogenesis and potential therapies for epilepsy.

Bioactive Peptide F2d Isolated from Rice Residue Exerts Antioxidant Effects via Nrf2 Signaling Pathway.

Studies have shown that the peroxidation caused by oxygen free radicals is an important reason of vascular endothelial dysfunction and multiple diseases. In this study, active peptides (F2ds) were isolated from the fermentation product of rice dregs and its antioxidant effects were approved. Human umbilical vein endothelial cells (HUVECs) stimulated by H2O2 were used to evaluate the antioxidation effect and its molecular mechanism in the oxidative stress model. F2d protected H2O2-induced damage in HUVECs in a dosage-dependent manner. F2d can reduce the expression of Keap1, promote the expression of Nrf2, and activate the downstream target HO-1, NQO1, etc. It means F2d can modulate the Nrf2 signaling pathway. Using Nrf2 inhibitor ML385 to block the Nrf2 activation, the protective function of F2d is partially lost in the damage model. Our results indicated that F2d isolated from rice exerts antioxidant effects via the Nrf2 signaling pathway in H2O2-induced damage, and the work will benefit to develop functional foods.

Dietary Supplementation of Octacosanol Improves Exercise-Induced Fatigue and Its Molecular Mechanism.

Several publications report that octacosanol (OCT) has different biological functions. This study was designed to evaluate the antifatigue effect and molecular mechanism of octacosanol (200 mg/(kg day)) in forced exercise-induced fatigue models of trained male C57BL/6 mice. Results showed that octacosanol ameliorated the mice's autonomic activities, forelimb grip strength, and swimming endurance, and the levels of liver glycogen (LG), muscle glycogen (MG), blood lactic acid (BLA), lactate dehydrogenase (LDH), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px) were also regulated. Gene analysis results showed that treatment with OCT upregulated 29 genes, while 38 genes were downregulated in gastrocnemius tissue. Gene ontology (GO) analyses indicated that these genes enriched functions in relation to myofibril, contractile fiber, and calcium-dependent adenosinetriphosphatase (ATPase) activity. Octacosanol supplementation significantly adjusted the messenger RNA (mRNA) and protein expression levels related to fatigue performance. Octacosanol has an observably mitigating effect in exercise-induced fatigue models, and its molecular mechanism may be related to the regulation of tripartite motif-containing 63 (Trim63), periaxin (Prx), calcium voltage-gated channel subunit α1 H (Cacna1h), and myosin-binding protein C (Mybpc3) expression.

New application of an old drug proparacaine in treating epilepsy via liposomal hydrogel formulation.

Proparacaine (PPC) is a previously discovered topical anesthetic for ophthalmic optometry and surgery by blocking the central Nav1.3. In this study, we found that proparacaine hydrochloride (PPC-HCl) exerted an acute robust antiepileptic effect in pilocarpine-induced epilepsy mice. More importantly, chronic treatment with PPC-HCl totally terminated spontaneous recurrent seizure occurrence without significant toxicity. Chronic treatment with PPC-HCl did not cause obvious cytotoxicity, neuropsychiatric adverse effects, hepatotoxicity, cardiotoxicity, and even genotoxicity that evaluated by whole genome-scale transcriptomic analyses. Only when in a high dose (50 mg/kg), the QRS interval measured by electrocardiography was slightly prolonged, which was similar to the impact of levetiracetam. Nevertheless, to overcome this potential issue, we adopt a liposome encapsulation strategy that could alleviate cardiotoxicity and prepared a type of hydrogel containing PPC-HCl for sustained release. Implantation of thermosensitive chitosan-based hydrogel containing liposomal PPC-HCl into the subcutaneous tissue exerted immediate and long-lasting remission from spontaneous recurrent seizure in epileptic mice without affecting QRS interval. Therefore, this new liposomal hydrogel formulation of proparacaine could be developed as a transdermal patch for treating epilepsy, avoiding the severe toxicity after chronic treatment with current antiepileptic drugs in clinic.

The prognostic value of an autophagy-related lncRNA signature in hepatocellular carcinoma.

BACKGROUND: lncRNA may be involved in the occurrence, metastasis, and chemical reaction of hepatocellular carcinoma (HCC) through various pathways associated with autophagy. Therefore, it is urgent to reveal more autophagy-related lncRNAs, explore these lncRNAs' clinical significance, and find new targeted treatment strategies. METHODS: The corresponding data of HCC patients and autophagy genes were obtained from the TCGA database, and the human autophagy database respectively. Based on the co-expression and Cox regression analysis to construct prognostic prediction signature. RESULTS: Finally, a signature containing seven autophagy-related lncRNAs (PRRT3-AS1, RP11-479G22.8, RP11-73M18.8, LINC01138, CTD-2510F5.4, CTC-297N7.9, RP11-324I22.4) was constructed. Based on the risk score of signature, Overall survival (OS) curves show that the OS of high-risk patients is significantly lower than that of low-risk patients (P = 2.292e-10), and the prognostic prediction accuracy of risk score (AUC = 0.786) is significantly higher than that of ALBI (0.532), child_pugh (0.573), AFP (0.5751), and AJCC_stage (0.631). Moreover, multivariate Cox analysis and Nomogram of risk score are indicated that the 1-year and 3-year survival rates of patients are obviously accuracy by the combined analysis of the risk score, child_pugh, age, M_stage, and Grade (The AUC of 1- and 3-years are 0.87, and 0.855). Remarkably, the 7 autophagy-related lncRNAs may participate in Spliceosome, Cell cycle, RNA transport, DNA replication, and mRNA surveillance pathway and be related to the biological process of RNA splicing and mRNA splicing. CONCLUSION: In conclusion, the 7 autophagy-related lncRNAs might be promising prognostic and therapeutic targets for HCC.

Usefulness of atherogenic index of plasma for estimating reduced eGFR risk: insights from the national health and nutrition examination survey.

AIMS: Previous studies have identified Atherogenic index of plasma (AIP) as a simple measure of atherosclerosis. Because atherosclerosis plays a role in the development of renal damage, our study aims to evaluate the effect of AIP on the risk of reduced eGFR and assess its usefulness to refine the risk stratification of reduced estimated glomerular filtration rate (eGFR). METHODS: Our study included 15,836 participants from the National Health and Nutritional Survey (NHANES) 2009-2016. Association was investigated by logistic regression. AIP was calculated as log (triglycerides/high-density lipoprotein cholesterol). Reduced eGFR was determined as eGFR < 60 ml/min per 1.73 m*2. RESULTS: The prevalence of reduced eGFR was 8.01%. In the full model, each SD increase of AIP leaded to 27.4% additional risk for reduced eGFR. After dividing AIP into quartiles, the fourth quartile had a 1.649 times risk than the first quartile. Moreover, smooth curve fitting suggested that the risk of reduced eGFR elevated linearly with the increase of AIP. Subgroup analysis demonstrated that the association between AIP and reduced eGFR was robust in sex, body mass index, hypertension, and diabetes subpopulation, but the association was significantly stronger in black race and people aged less than 50 years old. Additionally, AUC displayed an advancement when introducing AIP into established risk factors (0.875 cs. 0.897, P < 0.001), category-free net reclassification index (0.249, 95% CI: 0.192-0.306, P < 0.001) and integrated discrimination index (0.007, 95% CI: 0.004-0.009, P < 0.001) also suggested the improvement from AIP. CONCLUSION: The present work suggested a linear association between AIP and reduced eGFR. Furthermore, the results showed that the association was stronger in black race and people aged less than 50 years old. Most importantly, our work implicated the usefulness of AIP to refine the risk stratification of reduced eGFR.

Osmotic stress-triggered stomatal closure requires Phospholipase Dδ and hydrogen sulfide in Arabidopsis thaliana.

Osmotic stress is one of the main stresses seriously affects the growth and development of plants. Hydrogen sulfide (H2S) emerges as the third gaseous signal molecule to involve in the complex network of signaling events. Phospholipase Dδ (PLDδ), as signal enzyme, responds to many biotic or abiotic stress responses. In this study, the functions and the relationship of PLDδ and H2S in stomatal closure induced by osmotic stress were explored. Using the seedlings of ecotype (WT), PLDδ deficient mutant (pldδ), L-cysteine desulfhydrase (LCD) deficient mutant (lcd) and pldδlcd double mutant as materials, the Real-time quantitative PCR (RT-qPCR) and the stomatal aperture were analyzed. Osmotic stress induced the expressions of PLDδ and LCD. The H2S content and the activities of PLD and LCD ascended in WT under osmotic stress. The phenotypes of pldδ, lcd and pldδlcd were more sensitive to osmotic stress than WT. Compared with pldδ, the stomatal of lcd showed lower sensitivity to osmotic stress, and the stomatal aperture of pldδlcd was similar to that of lcd. Simultaneous application of PA and NaHS resulted in tighter closure of stomatal than application of either PA or NaHS alone. These results suggested that osmotic stress-triggered stomatal closure requires PLDδ and H2S in A. thaliana. LCD acted downstream of PLDδ to regulate the stomatal closure induced by osmotic stress.

Kaempferol Protects Cell Damage in In Vitro Ischemia Reperfusion Model in Rat Neuronal PC12 Cells.

Ischemic cerebral stroke is a severe neurodegenerative disease with high mortality. Ischemia and reperfusion injury plays a fundamental role in ischemic cerebral stroke. To date, the strategy for ischemic cerebral stroke treatment is limited. In the present study, we aimed to investigate the effect of kaempferol (KFL), a natural flavonol, on cell injury induced by oxygen and glucose deprivation (OGD) and reoxygenation (OGD-reoxygenation) in PC12 cells. We found that KFL inhibited OGD-induced decrease of cell viability and the increase of lactate dehydrogenase (LDH) release. OGD-induced activation of mitochondrial dysfunction, mitochondrial apoptotic pathway, and apoptosis was inhibited by KFL. KFL also reduced OGD-induced oxidative stress in PC12 cells. P66shc expression and acetylation were increased by OGD and KFL inhibited these changes. Upregulation of P66shc suppressed KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. Furthermore, KFL inhibited OGD-induced decrease of sirtuin 1 (SIRT1) expression and downregulation of SIRT1 blocked KFL-induced decrease of apoptosis, the decrease of LDH release, and the increase of cell viability. In summary, we identified that KFL exhibited a beneficial effect against OGD-induced cytotoxicity in an ischemia/reperfusion injury cell model. The findings suggest that KFL may be a promising choice for the intervention of ischemic stroke and highlighted the SIRT1/P66shc signaling.

Synergistic interaction of hyperuricemia and hypertension on reduced eGFR: insights from a general Chinese population.

OBJECTIVES: Hyperuricemia and Hypertension are two independent risk factors of renal function damage. Our research aimed to investigate the synergistic interaction between hyperuricemia and hypertension toward reduced eGFR. METHODS: Our analyses included 11,694 participants from a cross-sectional population-based Northeast China Rural Cardiovascular Health Study. Interaction was assessed on both multiplicative and additive scales. RESULTS: The prevalence of reduced estimated glomerular infiltration rate (eGFR) was 2.11% in our population. After adjustment of age, sex, race, education level, family income, current smoking and drinking status, body mass index, total cholesterol, high-density lipoprotein cholesterol, and diabetes, subjects with both hyperuricemia and hypertension suffered from a 11.004 (95% CI: 7.080-17.102) times risk of reduced eGFR than the healthy reference group, greater than that in participants with only hyperuricemia (5.741, 95% CI: 3.045-10.825) or hypertension (1.145, 95% CI: 0.764-1.715). Furthermore, additive interaction between hyperuricemia and hypertension was statistically significant and synergistic (relative excess risk due to interaction: 5.118, 95% CI: 0.611-9.624; the attributable proportion due to interaction: 0.465, 95% CI: 0.151-0.779; Synergy index: 2.047, 95% CI: 1.017-4.120). However, our results revealed no significant interaction on the multiplicative scale. CONCLUSIONS: Hyperuricemia and hypertension may have a synergistic interaction toward renal function loss in addition to their independent impacts. Our findings may provide a straightforward illustration which is easy for the public to realize the hazard of coexistent hypertension and hyperuricemia on renal injury.