Sodium butyrate ameliorated diabetic nephropathy-associated tubulointerstitial inflammation by modulating the tight junctions of renal tubular epithelial cells.

As one of the most significant pathological changes of diabetic nephropathy (DN), tubulointerstitial fibrosis (TIF) had a close relationship with tubulointerstitial inflammation (TI), and the occurrence of TI could have resulted from the disrupted tight junctions (TJs) of renal tubular epithelial cells (RTECs). Studies have demonstrated that sodium butyrate (NaB), a typical short chain fatty acid (SCFA), played an important regulatory role in intestinal TJs and inflammation. In this study, our in vivo and in vitro results showed that accompanied by TI, renal tubular TJs were gradually disrupted in the process of DN-related TIF. In HG and LPS co-cultured HK-2 cells and db/db mice, NaB treatment regained the TJs of RTECs via the sphingosine 1-phosphate receptor-1 (S1PR1)/AMPK signaling pathway, relieving inflammation. Small interfering RNA of S1PR1, S1PR1 antagonist W146 and agonist SEW2871, and AMPK agonist AICAR were all used to further confirm the essential role of the S1PR1/AMPK signaling pathway in NaB's TJ protection in RTECs in vitro. Finally, NaB administration not only improved the renal function and TIF, but also relieved the TI of db/db mice. These findings suggested that the use of NaB might be a potential adjuvant treatment strategy for DN-associated TIF, and this protective effect was linked to the TJ modulation of RTECs via the S1PR1/AMPK signaling pathway, leading to the improvement of TI.

Analysis of Risk Factors for Complications after Percutaneous Coronary Intervention in Patients with Acute ST-segment Elevation Myocardial Infarction.

Background: Acute ST segment elevation myocardial infarction (ASTEMI) is the most common and serious type of AMI, percutaneous coronary intervention (PCI) is currently the most commonly used approach for clinical treatment of ASTEMI. After PCI, patients with ASTEMI are very prone to various complications, which will seriously threaten their health and life safety. Objective: This study aims to analyze the risk factors for complications in patients with acute ST-segment elevation myocardial infarction (ASTEMI) treated with percutaneous coronary intervention (PCI). Methods: A total of 107 patients with ASTEMI who were subjected to PCI from October 2021 to December 2022 were selected as study subjects. Patients were divided into a safety group (no complications, n = 63) and a risk group (n = 45) based on the presence of postoperative complications. Baseline data (age, sex, etc.), Killip classification, left ventricular ejection fractions (LVEF), and routine blood test results were collected from patients in both groups for Logistic regression analysis to obtain relevant factors affecting the occurrence of post-PCI complications. Results: There were no differences between the safety group and the risk group in terms of sex, age, body mass index (BMI), Killip classification, and infarct site (P > .05). Compared with the safety group, the risk group exhibited a higher proportion of patients with multiple pre-existing diseases, LVEF < 40%, and number of coronary artery lesions ≥ 1, and higher levels of hs-CRP, NT-proBNP, HbA1c and Scr (P < .05). Logistic regression analysis results showed that multiple pre-existing diseases, hs-CRP, NT-proBNP, HbA1c, and Scr were relevant factors affecting the occurrence of post-PCI complications (P < .05). Conclusion: Multiple pre-existing diseases, hs-CRP, NT-proBNP, HbA1c, and Scr were all independent risk factors for the occurrence of post-PCI complications. Future clinical attention should be paid to these indicators in patients with ASTEMI in order to prevent post-PCI complications.

Increased interbrain synchronization and neural efficiency of the frontal cortex to enhance human coordinative behavior: A combined hyper-tES and fNIRS study.

Coordination is crucial for individuals to achieve common goals; however, the causal relationship between coordination behavior and neural activity has not yet been explored. Interbrain synchronization (IBS) and neural efficiency in cortical areas associated with the mirror neuron system (MNS) are considered two potential brain mechanisms. In the present study, we attempted to clarify how the two mechanisms facilitate coordination using hypertranscranial electrical stimulation (hyper-tES). A total of 124 healthy young adults were randomly divided into three groups (the hyper-tACS, hyper-tDCS and sham groups) and underwent modulation of the right inferior frontal gyrus (IFG) during functional near-infrared spectroscopy (fNIRS). Increased IBS of the PFC or neural efficiency of the right IFG (related to the MNS) was accompanied by greater coordination behavior; IBS had longer-lasting effects on behavior. Our findings highlight the importance of IBS and neural efficiency of the frontal cortex for coordination and suggest potential interventions to improve coordination in different temporal windows.

Resveratrol prevents Drp1-mediated mitochondrial fission in the diabetic kidney through the PDE4D/PKA pathway.

To explore the role of PDE4D in diabetic nephropathy (DN) and investigate whether resveratrol protects against DN via inhibiting PDE4D. Diabetic db/db mouse and glomerular mesangial cell line (GMCs) were used to investigate the role of PDE4D and the protective effect of resveratrol on renal fibrosis under high glucose (HG) environment. Resveratrol alleviated the progress of DN via inhibiting mitochondrial fragmentation and restoring the expression of PDE4D, PKA, phosphorylated Drp1-Ser637 and Drp1 in kidney of db/db mice. In HG-exposed GMCs, resveratrol treatment decreased the expression of PDE4D, increased PKA level, and inhibited Drp1-mediated mitochondrial fission. In contrast, PDE4D over-expression blunted the inhibitory effects of resveratrol on Drp1 expression and mitochondrial fission. Moreover, PKA inhibitor H89 blunted the effects of resveratrol on phosphorylated Drp1-Ser637 expression and mitochondrial fission in HG-treated GMCs. Inhibition of mitochondrial fission with Drp1 inhibitor Mdivi-1 alleviated mitochondrial dysfunction in GMCs under HG. These findings indicate PDE4D plays an important role in the process of DN. Resveratrol attenuates the development of DN by preventing mitochondrial fission through inhibiting PDE4D, which regulates the expression of phosphorylated Drp1-Ser637 directly.

Jingfang granules exert anti-psoriasis effect by targeting MAPK-mediated dendritic cell maturation and PPARγ-mediated keratinocytes cell cycle progression in vitro and in vivo.

BACKGROUND: Jingfang granules (JFG), derived from JingFangBaiDu San (JFBDS), are a traditional herbal formulas used for the treatment of respiratory tract infections. They were initially prescribed to treat skin disease, such as psoriasis in Chinese Taiwan, but are not widely used for psoriasis treatment in mainland China because of the lack of anti-psoriasis mechanism research. PURPOSES: The present study was designed to evaluate the anti-psoriasis effect of JFG and reveal the correlated mechanisms of JFG in vivo and in vitro using network pharmacology, UPLC-Q-TOF-MS technology and molecular biotechnology methods. RESULTS: An imiquimod-induced psoriasis-like murine model was used to verify the anti-psoriasis effect in vivo, with inhibition of lymphocytosis and CD3+CD19+B cell proliferation in the peripheral blood and prevention of the activation of CD4+IL17+T cells and CD11c+ MHC Ⅱ+ dendritic cells (DCs) in the spleen. Network pharmacology analysis demonstrated that the targets of the active components were significantly enriched in pathways involved in cancer, inflammatory bowel disease and rheumatoid arthritis, which were closely related to cell proliferation and immune regulation. The drug-component-target networks and molecular docking analysis demonstrated the active ingredients to be luteolin, naringin and 6'-feruloylnodakenin, which had a good binding affinity to PPARγ, p38a MAPK and TNF-a. Finally, UPLC-Q-TOF-MS analysis to validate the active ingredients in drug-containing serum and in vitro experiments showed that JFG inhibited the maturation and activation of BMDCs via the p38a MAPK signaling pathway and translocation of the agonist PPARγ into the nuclei to reduce the activity of NF-κB/STAT3 inflammatory signaling pathway in keratinocytes. CONCLUSIONS: Our study demonstrated that JFG improved psoriasis by inhibiting the maturation and activation of BMDCs and proliferation and inflammation of keratinocytes, which may facilitate the applications of JFG in anti-psoriasis therapy in clinical settings.

Visual tracking of label-free microplastics in wheat seedlings and their effects on crop growth and physiology.

The effects of microplastics on crop plants have attracted growing attention. However, little is known about the effects of microplastics and their extracts on the growth and physiology of wheat seedlings. In this study, hyperspectral-enhanced dark field microscopy and scanning electron microscopy were used to accurately track the accumulation of 200 nm label-free polystyrene microplastics (PS) in wheat seedlings. The PS accumulated along the root xylem cell wall and in the xylem vessel member and then moved toward to the shoots. In addition, lower concentration (≤ 5 mg·L-1) of microplastics increased root hydraulic conductivity by 80.6 %- 117.0 %. While higher PS treatment (200 mg·L-1) considerably decreased plant pigments content (chlorophyll a, b, and total chlorophyll) by 14.8 %, 19.9 %, and 17.2 %, respectively, and decreased root hydraulic conductivity by 50.7 %. Similarly, catalase activity was reduced by 17.7 % in root and 36.8 % in shoot. However, extracts from the PS solution showed no physiological effect on wheat. The result confirmed that it was the plastic particle, rather than the chemical reagents added in the microplastics, contributed to the physiological variation. These data will benefit to better understanding on the behavior of microplastics in soil plants, and to providing of convincing evidence for the effects of terrestrial microplastics.

Correction to: YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.

The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which has a close relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) plays an important role not only in regulating the fibrosis process but also in maintaining the mitochondrial function of pancreatic ß-cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG up-regulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose-cultured HK-2 cells and 8-weeks-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF.

YY1 was indispensable for the alleviation of quercetin on diabetic nephropathy-associated tubulointerstitial inflammation.

BACKGROUND: The emergence of tubulointerstitial inflammation (TI) could accelerate the development of tubulointerstitial fibrosis (TIF) of diabetic nephropathy (DN). Yin Yang 1 (YY1) was a new pro-inflammatory mediator and became the important target of DN-related TIF. Quercetin performed an effective role in anti-inflammation and was probable to bind to YY1. However, the role of YY1 in quercetin's anti-inflammatory effect on DN-related TIF was uncovered. PURPOSE: To investigate the potential effect and mechanism of quercetin against DN-related TI. STUDY DESIGN AND METHODS: The protein levels of YY1 were examined in the renal tubular epithelial cells (RTECs) of db/db mice and HG-cultured HK-2 cells. Molecular modeling studies and YY1 overexpression lentivirus vector were selected to further confirm the indispensable part of YY1 in quercetin's TI protection in vitro. Luciferase assay and chromatin immunoprecipitation (ChIP) assay were carried out to identify whether YY1 directly regulated IL-6/STAT3 signaling by binding to the IL-6 promoter in quercetin's TI protection in vitro. At last, the important role of YY1-mediated IL-6/STAT3 signaling in quercetin's TIF protection effect was further identified by using of YY1 overexpression lentivirus vector and IL-6 specific inhibitor tocilizumab. RESULTS: Along with the alleviated tubulointerstitial injury by quercetin in the RTECs of db/db mice and HK-2 cells stimulated by HG, YY1-mediated IL-6/STAT-3 pathway involved in TI protection of quercetin in vivo and in vitro. Quercetin bound to YY1 and decreased its protein expression, and YY1 directly suppressed IL-6 transcription by bounding to its promoter, resulting in the alleviation of inflammation by inactivating of IL-6/STAT-3 pathway in vitro. YY1-mediated IL-6/STAT-3 pathway was also indispensable for the alleviation of quercetin on DN-associated TIF. CONCLUSION: YY1 could not be absent from quercetin's anti-inflammatory effect on DN-associated TIF via alleviating IL-6/STAT-3 pathway mediated TI.

YY1 inactivated transcription co-regulator PGC-1α to promote mitochondrial dysfunction of early diabetic nephropathy-associated tubulointerstitial fibrosis.

The development of diabetic nephropathy (DN) could be promoted by the occurrence of tubulointerstitial fibrosis (TIF), which had a closely relationship with mitochondrial dysfunction of renal tubular epithelial cells (RTECs). As a key regulator of metabolic homeostasis, Yin Yang 1 (YY1) played an important role not only in regulating fibrosis process, but also in maintaining mitochondrial function of pancreatic ß cells. However, it was not clear whether YY1 participated in maintaining mitochondrial function of RTECs in early DN-associated TIF. In this study, we dynamically detected mitochondrial functions and protein expression of YY1 in db/db mice and high glucose (HG)-cultured HK-2 cells. Our results showed that comparing with the occurrence of TIF, the emergence of mitochondrial dysfunction of RTECs was an earlier even, besides the up-regulated and nuclear translocated YY1. Correlation analysis showed YY1 expressions were negatively associated with PGC-1α in vitro and in vivo. Further mechanism research demonstrated the formation of mTOR-YY1 heterodimer induced by HG upregulated YY1, the nuclear translocation of which inactivated PGC-1α by binding to the PGC-1α promoter. Overexpression of YY1 induced mitochondrial dysfunctions in normal glucose cultured HK-2 cells and 8-week-old db/m mice. While, dysfunctional mitochondria induced by HG could be improved by knockdown of YY1. Finally, downregulation of YY1 could retard the progression of TIF by preventing mitochondrial functions, resulting in the improvement of epithelial-mesenchymal transition (EMT) in early DN. These findings suggested that YY1 was a novel regulator of mitochondrial function of RTECs and contributed to the occurrence of early DN-associated TIF .

Fire Needle Combined Therapy or Surgery Therapy for Carbuncle of Neck? A Case Series.

Background: Skin carbuncle is a suppurative infection of adjacent multiple hair follicles and their surrounding tissues, mostly caused by Staphylococcus aureus. Skin carbuncle often occurs in the neck, the back, and other skin thicker parts. It can also spread to the subcutaneous tissue and cause extensive subcutaneous infection. It is especially common in people with low immunity such as diabetes, nephritis, and malnutrition. Patients and Methods: We reported four cases of carbuncle of the neck, three of which were treated with traditional Chinese medicine therapy based on fire needles combined with topical drugs, and the other one was treated by surgical incision and drainage, debridement, and dressing change. Results: All four cases achieved good therapeutic effects. The results showed that in the treatment of early carbuncle, compared with surgical treatment, fire needle therapy had less trauma, smaller prognosis scar, less cost, and faster recovery. However, when the carbuncle significantly expands or the deep tissue of the late carbuncle shows erosion necrosis, surgical debridement is necessary. Conclusion: The traditional Chinese medicine therapy based on the fire needle for the early treatment of carbuncle has important clinical significance, which is worthy of further study.

Successful Treatment in a Child with Refractory Periungual Warts by Local Hyperthermia: A Case Report.

Periungual wart is a kind of verruca vulgaris that occurs alongside or underlying the nails, which is challenging to treat and prone to recurrence, seriously affecting the quality of patients' life. We report a 6-year-old boy with periungual warts who had experienced various treatments with no improvement and even worsening. Therefore, we tried to treat the patient with local hyperthermia which uses a patented device that has an infrared emission source. The heat generated by infrared rays acts on the local skin surface. The mechanism of this therapy may be to establish a specific immune response against human papillomavirus-infected tissues, thereby facilitating the clearance of human papillomavirus at irradiated and non-irradiated sites. Local hyperthermia has the advantages of non-contact, safety, noninvasive, less pain, and so on. After 5 treatments, the irradiated periungual warts completely cleared after 2 weeks. The unirradiated sites were almost cured after 7 weeks. This case suggests that local thermotherapy has shown great advantages in the treatment of these refractory periungual warts and offers a new and effective therapy in patients with periungual warts.

Lipidomics reveals significant alterations associated with exclusive enteral nutrition treatment in adult patients with active Crohn's disease.

Background: Crohn's disease (CD), a type of inflammatory bowel disease, is a chronic idiopathic disorder of the gastrointestinal tract with an increasing global incidence. Exclusive enteral nutrition (EEN) is a diet therapy that is effective in the management of active CD with unknown etiology. Lipid metabolism plays an important role in CD and may be associated with EEN treatment. This study compared the plasma lipid profiles before and after EEN in adults with active CD to those of healthy controls (HCs). Methods: Eleven adult patients with active CD who received enteral nutrition formula treatment for 12 weeks were included, along with 17 HCs. The profiles of 869 plasma lipid species were measured, and inflammatory and nutrition-associated indices were evaluated in the patients. Results: Nine patients achieved clinical remission following 12 weeks of EEN treatment, and four achieved mucosal healing. Before EEN, 80 lipid species and 17 lipid classes were significantly different between patients with CD and HCs. After EEN treatment, 103 lipid species and 12 lipid classes were significantly different between patients with CD and HCs. Significant changes in 7 lipid classes and 38 lipid species were observed between the pre- vs. post-treatment CD patients. The levels of simplified glucosylceramide series, monogalactosyldiacylglycerol, phosphatidylinositol, phosphatidylserine, and phosphatidylcholine increased, while those of phosphatidylglycerol and phosphatidylinositol diphosphate decreased significantly after EEN. These lipid classes and species were associated with the inflammatory and nutritional indices. Pathway analysis suggested the metabolism of arachidonic acid, glycerophospholipids, linoleate, and phosphatidylinositol phosphate was related to the EEN mechanism. Conclusions: EEN induces alterations in multiple lipid classes and species, leading to clinical improvements. Lipid metabolism may be involved in the EEN anti-inflammatory effect.

General toxicity and genotoxicity of alternariol: a novel 28-day multi-endpoint assessment in male Sprague-Dawley rats.

Alternariol (AOH) is one of the toxins of Alternaria, and it has been widely detected in a variety of foods. It has been reported to be cytotoxic, dermally toxic, genotoxic, and potentially carcinogenic in vitro. However, in vivo toxicity data are lacking. This study used a novel in vivo 28-day multi-endpoint (Pig-a assay + micronucleus test + comet assay) genotoxicity evaluation system to evaluate the general toxicity and genotoxicity of AOH. A total of 42 male Sprague-Dawley rats were randomly distributed into three AOH-treated groups (5.51, 10.03, and 22.05 µg/kg bw), one AOH high-dose recovery group (AOH-HR, 22.05 µg/kg bw), one positive control group (N-ethyl-N-nitrosourea, 40 mg/kg bw), and two vehicle control groups (corn oil and PBS). Treatments were administered by oral gavage for 28 consecutive days. Histopathological lesions were observed in the liver, kidney, and spleen in all AOH-treated groups. No statistical difference was found in each genotoxicity index within 28 days in the AOH-treated groups compared with those in the corn oil group. On day 42, in the AOH-HR group, the rate of Pig-a mutant phenotype reticulocytes (RETCD59-) significantly increased. On day 56, both RETCD59- and the rate of Pig-a mutant phenotype erythrocytes (RBCCD59-) were significantly reduced. These findings indicated that AOH might cumulatively induce genetic mutations.

Sequential washing and eluent regeneration with agricultural waste extracts and residues for facile remediation of meta-contaminated agricultural soils.

Washing with organic acids and dissolved organic carbon (DOC) is a promising technique for effective removal of potentially toxic metals from agricultural soils and the two key factors are the screening of inexpensive, high-efficiency, and environmentally friendly washing agents and the safe treatment of waste eluent. We used extracts from agro-forestry wastes (pineapple peel, lemon peel, grapefruit peel and gardening crabapple fruit) to develop a facile two-stage sequential washing method (extracts and/or citric acid (CA) and coupled with extracts) and regenerated waste eluent. The washing efficiencies of Cd and Cu were significantly increased by pineapple peel (PP) using two-stage sequential washing with the sequence of PP + CA-PP > CA-PP > PP-PP. The potential pollution risk from soil Cd was lowered by 33.0% from moderate to low risk, and soil nutrient contents increased. 80.9% of Cd and 81.3% of Cu in waste eluent were efficiently removed by the PP residues. The removal mechanisms of metals in soils and eluents by PP washing agents and residues can be attributed to acid activation, cation exchange and complexation between metal ions and carboxyl groups. Therefore, the PP extracts and residues are potentially suitable for the removal of Cd and Cu from polluted agricultural soils and washing waste eluents.

[Formulation optimization of emodin nanostructured lipid carriers by Box-Behnken response surface method and in vitro quality evaluation].

Emodin nanostructured lipid carriers(ED-NLC) were prepared and their quality was evaluated in vitro. Based on the results of single-factor experiments, the ED-NLC formulation was optimized by Box-Behnken response surface method with the dosages of emodin, isopropyl myristate and poloxamer 188 as factors and the nanoparticle size, encapsulation efficiency and drug loading as evaluation indexes. Then the evaluation was performed on the morphology, size and in vitro release of the nanoparticles prepared by emulsification-ultrasonic dispersion method in line with the optimal formulation, i.e., 3.27 mg emodin, 148.68 mg isopropyl myristate and 173.48 mg poloxamer 188. Under a transmission electron microscope(TEM), ED-NLC were spherical and their particle size distribution was uniform. The particle size of ED-NLC was(97.02±1.55) nm, the polymer dispersion index 0.21±0.01, the zeta potential(-38.96±0.65) mV, the encapsulation efficiency 90.41%±0.56% and the drug loading 1.55%±0.01%. The results of differential scanning calorimeter(DSC) indicated that emodin may be encapsulated into the nanostructured lipid carriers in molecular or amorphous form. In vitro drug release had obvious characteristics of slow release, which accorded with the first-order drug release equation. The fitting model of Box-Behnken response surface methodology was proved accurate and reliable. The optimal formulation-based ED-NLC featured concentrated particle size distribution and high encapsulation efficiency, which laid a foundation for the follow-up study of ED-NLC in vivo.

Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states.

In humans, tissue injury and depression can both cause pain hypersensitivity, but whether this involves distinct circuits remains unknown. Here, we identify two discrete glutamatergic neuronal circuits in male mice: a projection from the posterior thalamic nucleus (POGlu) to primary somatosensory cortex glutamatergic neurons (S1Glu) mediates allodynia from tissue injury, whereas a pathway from the parafascicular thalamic nucleus (PFGlu) to anterior cingulate cortex GABA-containing neurons to glutamatergic neurons (ACCGABA→Glu) mediates allodynia associated with a depression-like state. In vivo calcium imaging and multi-tetrode electrophysiological recordings reveal that POGlu and PFGlu populations undergo different adaptations in the two conditions. Artificial manipulation of each circuit affects allodynia resulting from either tissue injury or depression-like states, but not both. Our study demonstrates that the distinct thalamocortical circuits POGlu→S1Glu and PFGlu→ACCGABA→Glu subserve allodynia associated with tissue injury and depression-like states, respectively, thus providing insights into the circuit basis of pathological pain resulting from different etiologies.

Effects of Tart Cherry Powder on Serum Uric Acid in Hyperuricemia Rat Model.

Hyperuricemia, as a critical risk factor for various adverse clinical outcomes, shows a trend of increasing prevalence among young-aged population. Dietary adjuvant therapy by function foods, such as tart cherry, is promising. Thus, effects of tart cherry powder specialized in hyperuricemia were explored via establishing a hyperuricemia model in Sprague Dawley rats by cotreatment with oteracil potassium and adenine. The results indicated that low dose of tart cherry powder (0.17 g/kg·bw) showed effects on hyperuricemia by slightly decreasing serum uric acid and improving kidney injury, whereas high dose of tart cherry powder (0.50 g/kg·bw) could merely alleviate kidney injury. Meanwhile, adenosine deaminase activity rather than xanthine oxidase activity was affected at low dose, which reveals low dose of tarty cherry powder may be beneficial to hyperuricemia through reduction of ADA activity, and its reported potentials on antioxidation or anti-inflammation provide clues for further study.

A somatosensory cortex input to the caudal dorsolateral striatum controls comorbid anxiety in persistent pain.

Chronic pain and anxiety symptoms are frequently encountered clinically, but the neural circuit mechanisms underlying the comorbid anxiety symptoms in pain (CASP) in context of chronic pain remain unclear. Using viral neuronal tracing in mice, we identified a previously unknown pathway whereby glutamatergic neurons from layer 5 of the hindlimb primary somatosensory cortex (S1) (Glu), a well-known brain region involved in pain processing, project to GABAergic neurons in the caudal dorsolateral striatum (GABA). In a persistent inflammatory pain model induced by complete Freund's adjuvant injection, enhanced excitation of the Glu→GABA pathway was found in mice exhibiting CASP. Reversing this pathway using chemogenetic or optogenetic approaches alleviated CASP. In addition, the optical activation of Glu terminals in the cDLS produced anxiety-like behaviors in naive mice. Overall, the current study demonstrates the putative importance of a novel Glu→GABA pathway in controlling at least some aspects of CASP.

[Preparation and characterization of glycyrrhetinic acid-modified nano graphene oxide drug delivery system].

In this study,a nano drug delivery system GA-DTX-NGO which could be used for liver tumor photothermal and chemotherapy was prepared and characterized,with docetaxel(DTX) as model drug,glycyrrhetinic acid(GA) as the target molecule,and nano graphene oxide(NGO) as the photosensitizer. Firstly,GA-NGO nanocomposites were synthesized by the amidation reaction,and then GA-DTX-NGO was prepared by ultrasonic dispersion method. The encapsulation efficiency and drug loading ratio were determined by high performance liquid chromatography(HPLC) and ultracentrifugation; the morphology was observed by transmission electron microscopy(TEM). The photothermal conversion test was carried out by laser irradiation at 808 nm and the drug release test in vitro was performed using reverse dialysis. Finally,the effect of GA-DTX-NGO on SMMC-7721 liver tumor cells proliferation was determined by using MTT assay. The results showed that GA-DTX-NGO had good water dispersibility,and TEM results showed a lamellar structure with about 200 nm in diameter. The encapsulation efficiency and drug loading ratio of GA-DTX-NGO were(98. 89 ± 0. 07) % and(64. 74±0. 26) %,respectively. GA-DTX-NGO had strong photothermal conversion performance under 808 nm of laser irradiation. The drug release test in vitro results showed GA-DTX-NGO had obvious sustained-release effects and temperature-dependent release characteristics. The results of cell assay showed that GA-DTX-NGO could effectively inhibit the proliferation of SMMC 7721 cells in a concentration-and time-dependent manner,and the inhibitory effect was enhanced after combination with the near-infrared therapy. In conclusion,the preparation process of GA-DTX-NGO nano drug delivery system is feasible,which could provide some theoretical basis for further study of photothermal and chemotherapy on liver tumor.

YY1: A novel therapeutic target for diabetic nephropathy orchestrated renal fibrosis.

BACKGROUND: Renal fibrosis promotes the development of diabetic nephropathy (DN). A growing number of studies have reported that Yin Yang 1 (YY1), which is involved in cellular proliferation and differentiation, plays a crucial role in the pathogenesis of many diseases, such as pulmonary fibrosis, hepatic steatosis and cancer. METHODS: We detected the expression of YY1 under various glucose concentration and time gradient conditions. Rapamycin was used to verify the mTORC1/p70S6K/YY1 signaling pathway in HK-2 cells. We used db/db mice to examine the connection between renal fibrosis and YY1. A luciferase assay and chromatin immunoprecipitation (ChIP) assay were used to identify whether YY1 directly regulated α-SMA by binding to the α-SMA promoter. RNA silencing and overexpression were performed by using a YY1 expression/knockdown plasmid to investigate the function of YY1 in renal fibrosis of DN. RESULTS: YY1 expression and subsequent nuclear translocation were upregulated in a glucose- and time-dependent manner via the mTORC1/p70S6K signaling pathway in HK-2 cells. YY1 expression and nuclear translocation was significantly upregulated in db/db mice. Furthermore, YY1 upregulated α-SMA expression and activity in high-glucose-cultured HK-2 cells. Overexpression of YY1 promoted renal fibrosis in db/m mice mainly by upregulating α-SMA expression and inducing epithelial-mesenchymal transition (EMT) in vitro and in vivo. Finally, downregulation of YY1 reversed renal fibrosis by improving EMT in vivo and in vitro. CONCLUSIONS: These results reveal that upregulation of YY1 plays a critical role in HG-induced deregulation of EMT-associated protein expression, which finally results in renal fibrosis of DN. Therefore, decreasing YY1 expression might represent a new therapeutic target for diabetic nephropathy-induced renal fibrosis.