Water Extract from Brown Strain of Flammulina velutipes Alleviates Cisplatin-Induced Acute Kidney Injury by Attenuating Oxidative Stress, Inflammation, and Autophagy via PI3K/AKT Pathway Regulation.

One of the most popular edible mushrooms in the world, Flammulina velutipes, has been shown to possess pharmacological properties such as anti-inflammatory and antioxidant properties. However, the potential activity of the brown strain of F. velutipes, a hybrid between the white and yellow strains, has not been thoroughly investigated. Numerous studies have been conducted in recent years to determine whether natural products can aid in improving or treating kidney diseases. In this study, we focused on the renoprotective effects of the brown strain of F. velutipes on cisplatin-induced acute kidney injury (AKI) in mice. Mice were pretreated with water extract from the brown strain of F. velutipes (WFV) from day 1 to day 10, with a single-dose intraperitoneal injection of cisplatin on day 7 to induce AKI. Our results demonstrated that WFV administration resulted in a reduction in weight loss and the amelioration of renal function and renal histological changes in mice with cisplatin-induced AKI. WFV improved antioxidative stress and anti-inflammatory capacity by increasing antioxidant enzymes and decreasing inflammatory factors. The expression of related proteins was determined via Western blot analysis, which showed that WFV could improve the expression of apoptosis and autophagy. We used the PI3K inhibitor Wortmannin and found that WFV achieved a protective effect by modulating the PI3K/AKT pathway and the expression of autophagy. Overall, WFV as a natural substance could be used as a new therapeutic agent for AKI.

Cluster-based text mining for extracting drug candidates for the prevention of COVID-19 from the biomedical literature.

Objective: The coronavirus disease 2019 (COVID-19) health crisis that began at the end of 2019 made researchers around the world quickly race to find effective solutions. Related literature exploded and it was inevitable that an automated approach was needed to find useful information, namely text mining, to overcome COVID-19, especially in terms of drug candidate discovery. While text mining methods for finding drug candidates mostly try to extract bioentity associations from PubMed, very few of them mine with a clustering approach. The purpose of this study was to demonstrate the effectiveness of our approach to identify drugs for the prevention of COVID-19 through literature review, cluster analysis, drug docking calculations, and clinical trial data. Methods: This research was conducted in four main stages. First, the text mining stage was carried out by involving Bidirectional Encoder Representations from Transformers for Biomedical to obtain vector representation of each word in the sentence from texts. The next stage generated the disease-drug associations, which were obtained from the correlation between disease and drug. Next, the clustering stage grouped the rules through the similarity of diseases by utilizing Term Frequency-Inverse Document Frequency as its feature. Finally, the drug candidate extraction stage was processed through leveraging PubChem and DrugBank databases. We further used the drug docking package AUTODOCK VINA in PyRx software to verify the results. Results: Comparative analyses showed that the percentage of findings using mining with clustering outperformed mining without clustering in all experimental settings. In addition, we suggest that the top three drugs/phytochemicals by drug docking analysis may be effective in preventing COVID-19. Conclusions: The proposed method for text mining utilizing the clustering method is quite promising in the discovery of drug candidates for the prevention of COVID-19 through the biomedical literature.

Combination of Autologous Fat Grafting and Negative-Pressure Wound Therapy for the Treatment of Scalp Linear Scleroderma.

ABSTRACT: Scalp linear scleroderma (LSc) is a subtype of localized scleroderma which typically affects young patients and which can be severely disfiguring. Traditional treatment options include bone grafting or tissue expansion. in this report, we present the case of a patient with scalp LSc successfully treated with scar release, autologous fat grafting, and negative-pressure wound therapy (NPWT). A 55-year-old female, with a history of craniectomy for a benign sellar tumor 10 years previously, developed LSc over the frontal scalp with exposure of titanium plates and screws. She was treated with removal of metalwork, scar release, autologous fat grafting from the abdominal wall and immediate application of NPWT. At 3-month postoperative follow-up, the appearance of the depressed lesion and of its margins had significantly improved. Our experience suggests that the combination of autologous fat grafting and NPWT is an effective treatment modality for scalp LSc.

A Stepwise Approach to the "Frozen Neck" for Secondary Microsurgical Reconstruction.

Supplemental Digital Content is available in the text.

Bioactivities and action mechanisms of active compounds from Hottuynia cordata Thunb on human lung cancer cells.

BACKGROUND: Lung cancer is the leading cause of death in Taiwan for years. Besides the currently used chemotherapy, herbal medicine may play a role in the treatment of lung cancer. Hottuynia cordata Thunb (HC), one of the frequently used herbal medicine in Taiwan, has been widely used in various diseases. Review from literatures, HC has many effects, including anti-inflammatory, anti-viral, anti-bacterial, anti-SARS, and anti-tumor activities. However, there is no literatures describe its active compounds on lung cancer. This present study aims to evaluate the possible effect and action mechanism of active compounds from HC (aristolactam BII, aristolactam AII, and noraristolodione) on lung cancer. A549 lung cancer cell line was used to evaluate the effects of HC on the cell viability and possible anti-tumor effects. METHODS: We used A549 cells in the evaluation of anticancer activity. Cell viability, cell cycle, cell apoptosis and apoptosis related protein expression were studied. RESULTS: Active compounds from HC significantly inhibited A549 cell viability and induced accumulation of cell cycle at S or G2/M phase on A549 cells in a concentration-dependent manner, and induced A549 arrest at S or G2/M phase via increasing p21, p27, p53 and reducing cyclin-E, -A, cyclin-dependent kinase 2 (CDK2), cdc-2 (CDK1) protein expression. Additionally, HC induced A549 cell late apoptosis by up-regulating caspase-3, -8, Bax and decreasing Bcl-2 protein expression. CONCLUSIONS: The anti-tumor effects of aristolactam BII, aristolactam AII, and noraristolodione on human lung carcinoma A549 cells were via cell cycle arrest and apoptosis.

In vivo microdialysis and in vitro HPLC analysis of the impact of paeoniflorin on the monoamine levels and their metabolites in the rodent brain.

BACKGROUND: Paeoniflorin (PF) possesses several effects such as analgesic, the anti-spasmodic effect on smooth muscle. It protects the cardiovascular system and reveals the neuroprotective effect on cerebral ischemia. Monoamine system has been identified to have complex regulatory effects in pain signaling. There are no reports regarding the impact of PF on monoamine levels in the rodent brain by microdialysis. In this study, the effects of PF on monoamines and their metabolites in the rodent brain using in vivo microdialysis and in vitro high performance liquid chromatography (HPLC) analysis. METHODS: Male S.D. rats were anesthetized, fixed onto the stereotaxic instrument to identify the positions of corpus striatum and cerebral cortex. Drilled a hole in the skull of anesthetic rats and proceeded microdialysis, and gave PF (100 µg, i.c.v.). Collected the dialysate and the concentration of monoamines and their metabolites in dialysate and analyzed with HPLC-ECD. Male ICR mice were administered with PF (96 µg, i.c.v.) and with Ringer solution as a control. After 20 mins of administration, the mice were cut off the brain immediately and separated into eight regions according to the method of Glowinski. Added extraction solution to each region, homogenized and extracted for further procedure. The extract was centrifuged, sucked the transparent layer and centrifuged once more. The transparent layer was filtered with a 0.22 µm nylon filter and analyzed with HPLC-ECD (electrochemical detection). RESULTS: PF increased the content of DOPAC and NE in the cortex, and increased the content of NE and decreased the content of 5-HT in the medulla of the homogenized mice brain tissue. By microdialysis, PF increased the content of DOPAC and 5-HIAA in anesthetic rat cortex and expanded the content of DOPAC, HVA, and 5-HIAA in anesthetic rat striatum. CONCLUSIONS: It reveals that PF could activate the release of monoamines and increase their metabolites in the rodent brain.

Pipoxolan Exhibits Antitumor Activity Toward Oral Squamous Cell Carcinoma Through Reactive Oxygen Species-mediated Apoptosis.

Pipoxolan is frequently prescribed as a smooth muscle relaxant. Pipoxolan has also been shown to have anticancer activity. Our study investigated whether pipoxolan induced apoptosis in oral squamous cell carcinoma (OSCC). Cell cytotoxicity was evaluated by the MTT assay. Cell apoptosis and cell-cycle distribution were measured by annexin V/propidium iodide (PI) double staining and flow cytometry, respectively. Apoptotic-related proteins were assessed by western blotting. Reactive oxygen species (ROS) generation and mitochondrial membrane potential (MMP) were measured with fluorescent probes. Following exposure of TW206 OSCC cells to pipoxolan, a time-dependently decrease in MMP and an increase in ROS were observed. However, these effects were significantly abrogated by the free radical scavenger N-acetyl-L-cysteine. Since high levels of ROS were produced early in the treatment, intracellular ROS seemed to play a key role in pipoxolan-induced apoptosis. In HSC-3 OSCC cells, our results demonstrated that pipoxolan treatment caused a time-dependent increase of protein expression of active caspase-3 and -9, cytosolic cytochrome c, cleavage of poly (ADP-ribose) polymerase, and B-cell lymphoma 2 (BCL2)-like protein 4 (BAX). However, expression of BCL2 itself was reduced. Clearly, such an increase in BAX/BCL2 ratio would be associated with apoptosis. In addition, pipoxolan markedly suppressed the protein expression of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K) and phosphorylation of protein kinase B (AKT). These data suggest that pipoxolan acts against HSC-3 in vitro via intrinsic apoptotic signaling pathways, and inhibition of PI3K/AKT signaling.

Pipoxolan inhibits CL1-5 lung cancer cells migration and invasion through inhibition of MMP-9 and MMP-2.

Pipoxolan has been reported to have antitumor activity. However, the effects of pipoxolan on lung cancer cell metastasis remains unclear. This study examined the anti-metastatic effects of pipoxolan on lung adenocarcinoma cancer cells (i.e. CL1-5, CL1-0, and A549) and its underlying molecular mechanisms. Firstly, CL1-5 cell migration was markedly suppressed by pipoxolan when examined by wound scratch assay. Furthermore, transwell and matrigel invasion assays revealed that pipoxolan inhibited lung cancer cells (i.e. CL1-5, CL1-0, and A549) migration/invasion, and showed more sensitive to CL1-5 cell. Therefore, the anti-metastatic effects from pipoxolan have been focused on CL1-5 lung cancer cells. Secondly, these observations have been associated with the reduction in the activities and expressions of matrix metalloproteinase (MMP)-2 and -9 in CL1-5 lung cancer cells. Lastly, pipoxolan administration significantly inhibited phosphorylation c-Jun N-terminal kinase (p-JNK), and p38 MAP Kinase (MAPK) of CL1-5 cells. Based on these results, our results showed that management CL1-5 cells with pipoxolan down-regulated phosphorylation JNK and p38, and then, MMP-2 and -9. These results suggest that pipoxolan might have a new therapeutic potential for anti-metastatic effects in lung cancer cells.

Anti-inflammatory activities of cardamonin from Alpinia katsumadai through heme oxygenase-1 induction and inhibition of NF-κB and MAPK signaling pathway in the carrageenan-induced paw edema.

Cardamonin is a chalcone isolated from Alpinia katsumadai. This study is aimed to evaluate treatment of cardamonin decreased the paw edema at the 5th hour after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT) and superoxide dismutase (SOD) in the anti-inflammatory test. We also demonstrated that cardamonin significantly attenuated the malondialdehyde (MDA) level in the edema paw at the 5th hour after Carr injection. Cardamonin decreased the nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), and IL-6 levels on the serum level at the 5th hour after Carr injection. Western blotting revealed that cardamonin decreased Carr-induced inducible nitric oxide synthase (iNOS), cycloxyclase (COX-2), nuclear factor-κB (NF-κB) and MAPK [extracellular signal-regulated protein kinase (ERK), c-Jun NH(2)-terminal kinase (JNK), p38] expressions and increased heme oxygenase-1 (HO-1) expressions at the 5th hour in the edema paw. The anti-inflammatory mechanisms of cardamonin might be related to the decrease in the level of MDA, iNOS, COX-2, NF-κB, and MAPK and induction of the HO-1 expression in the edema paw via increasing the activities of CAT and SOD in the edema paw through the suppression of NO, TNF-α, IL-1ß, and IL-6.

Antioxidant and anti-inflammatory properties of Taiwanese yam (Dioscorea japonica Thunb. var. pseudojaponica (Hayata) Yamam.) and its reference compounds.

Dioscorea japonica Thunb. var. pseudojaponica (DP) is consumed as food and widely used in traditional Chinese medicine in Taiwan. The aims of this study are to investigate the antioxidant and anti-inflammatory effects of ethanol extract of DP (EDP) and its reference compounds. Fingerprint chromatogram from HPLC indicated that EDP contains gallic acid and vanillic acid. EDP was evaluated for its antioxidant effects and LPS-induced nitrite oxide (NO) production in RAW264.7 cells. EDP decreased the LPS-induced NO production and expressions of iNOS and COX-2 in RAW264.7 cells. In-vivo anti-inflammatory activities of EDP were assessed in mouse paw oedema induced by λ-carrageenan (Carr). We investigated the antioxidant mechanism of EDP via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the oedematous paw. The results showed that EDP might be a natural antioxidant and anti-inflammatory agent.

Analgesic and anti-inflammatory bioactivities of eburicoic acid and dehydroeburicoic acid isolated from Antrodia camphorata on the inflammatory mediator expression in mice.

Eburicoic acid (TR1) and dehydroeburicoic acid (TR2), an active ingredient from Antrodia camphorata (AC) solid-state culture, were evaluated for analgesic and anti-inflammatory effects. Treatment with TR1 and TR2 significantly inhibited a number of acetic acid-induced writhing responses and formalin-induced pain in the late phase. In the anti-inflammatory test, TR1 and TR2 decreased paw edema at the fourth and fifth hour after λ-carrageenan (Carr) administration and increased the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) in the paw edema tissue. We also demonstrated that TR1 and TR2 significantly attenuated the malondialdehyde (MDA), nitric oxide (NO), tumor necrosis factor (TNF-α), and interleukin-1ß (IL-1ß) levels in either edema paw or serum at the fifth hour after Carr injection. Western blotting revealed that TR1 and TR2 decreased Carr-induced inducible nitric oxide synthase (iNOS) and cycloxyclase (COX-2) expressions at the fifth hour in paw edema. Treatment with TR1 and TR2 also diminished neutrophil infiltration into the paw edema at the fifth hour. The present study suggests that the anti-inflammatory mechanisms of TR1 and TR2 might be related to the decrease of inflammatory cytokines and an increase of antioxidant enzyme activity.

Antioxidant and anti-inflammatory activities of aqueous extract of Centipeda minima.

ETHNOPHARMACOLOGICAL RELEVANCE: Centipeda minima (L.) is traditionally used in Chinese folk medicine for the treatments of rhinitis, sinusitis, relieving pain, reducing swelling, and treating cancer for a long history in Taiwan. However, there is no scientific evidence which supports the use in the literature. AIM OF THE STUDY: The aim of this study was to evaluate the antioxidant and anti-inflammatory activities of the aqueous extract of Centipeda minima (ACM). MATERIALS AND METHODS: The following activities were investigated: antioxidant activities [2,2'-azino-bis (3-ethylbenzothiazoline-6-sulphonic acid) (ABTS), DPPH (1,1-diphenyl-2-picrylhydrazyl)], and anti-inflammatory [lipopolysaccharide (LPS) induced nitric oxide (NO) production in RAW264.7 macrophages and paw-edema induced by λ-carrageenan (Carr)]. We also investigated the anti-inflammatory mechanism of ACM via studies of the activities of catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) and the levels of malondialdehyde (MDA) in the edema paw. Serum NO, tumor necrosis factor α (TNF-α), and interleukin-1ß (IL-1ß) were also measured in vivo. In HPLC analysis, the fingerprint chromatogram of ACM was established. RESULTS: ACM showed the highest TEAC and DPPH radical scavenging activities, respectively. ACM also had highest contents of polyphenol and flavonoid contents. We evaluated that ACM and the reference compound of protocatechualdehyde and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Administration of ACM showed a concentration dependent inhibition on paw edema development after Carr treatment in mice. The anti-inflammatory effects of ACM could be via NO, TNF-α, and IL-1ß suppressions and associated with the increase in the activities of antioxidant enzymes. Western blotting revealed that ACM decreased Carr-induced inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions. CONCLUSIONS: Anti-inflammatory mechanisms of ACM might be correlated to the decrease in the level of Malondialdehyde (MDA), iNOS, and COX-2 via increasing the activities of CAT, SOD, and GPx in the edema paw. Overall, the results showed that ACM demonstrated antioxidant and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.

Antioxidant, Antinociceptive, and Anti-Inflammatory Activities from Actinidia callosa var. callosa In Vitro and In Vivo.

Actinidia callosa var. callosa has been widely used to treat antipyretic, analgesic, anti-inflammation, abdominal pain, and fever in Taiwan. The aim of this study was to evaluate the antioxidant, antinociceptive, and anti-inflammatory lipopolysaccharide-(LPS-)induced nitric oxide (NO) production in RAW264.7 macrophages and pawedema induced by λ-carrageenan activities of the methanol extract from A. callosa. In HPLC analysis, the fingerprint chromatogram of ethyl-acetate fraction of A. callosa (EAAC) was established. EAAC showed the highest TEAC and DPPH radical scavenging activities, respectively. We evaluated that EAAC and the reference compound of catechin and caffeic acid decreased the LPS-induced NO production in RAW264.7 cells. Treatment of male ICR mice with EAAC significantly inhibited the numbers of acetic acid-induced writhing response and the formalin-induced pain in the late phase. Administration of EAAC showed a concentration-dependent inhibition on paw edema development after Carr treatment in mice. Anti-inflammatory mechanisms of EAAC might be correlated to the expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and heme oxygenase-1 (HO-1) in vitro and in vivo. Overall, the results showed that EAAC demonstrated antioxidant, antinociceptive, and anti-inflammatory activity, which supports previous claims of the traditional use for inflammation and pain.

Ameliorative Effects of Scopoletin from Crossostephium chinensis against Inflammation Pain and Its Mechanisms in Mice.

Scopoletin exists in nature as an anti-oxidant, hepatoprotective, and anti-inflammatory activities reagent. In this study, we have investigated the analgesic effects of the scopoletin using the models of acetic acid-induced writhing response and the formalin test, the anti-inflammatory effects of scopoletin using model of λ-carrageenan (Carr)-induced paw edema. The treatment of ICR mice with scopoletin inhibited the numbers of writhing response and the formalin-induced pain in the late phase. This study demonstrated that the administration of scopoletin resulted in the reduction of Carr-induced mice edema, and it increased the activities of superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) after Carr injection. We also demonstrated scopoletin significantly attenuated the malondialdehyde (MDA) level in the edema paw after Carr injection. Scopoletin decreased the NO, tumor necrosis factor (TNF-α) and prostaglandin E2 (PGE(2)) levels on serum after Carr injection. Scopoletin decreased Carr-induced inducible NO synthase (iNOS) and cyclooxygenase-2 (COX-2) expressions in the edema paw. These anti-inflammatory mechanisms of scopoletin might be related to the decrease in the level of MDA via increasing the activities of SOD, CAT, and GPx in the edema paw. Also, scopoletin could affect the production of NO, TNF-α, and PGE(2), and therefore affect the anti-inflammatory effects.

Lose weight with traditional chinese medicine? Potential suppression of fat mass and obesity-associated protein.

Overweight and obesity are common health problems in modern society, particularly in developed countries. Excessive body mass has been linked to numerous diseases, such as cardiovascular diseases, diabetes, and cancer. Fat mass and obesity-associated protein (FTO) activity have direct impact on food intake and results in obesity. Inhibition of FTO activity may cause weight loss and reduce obese-linked health risks. We investigated the potential weight loss effects of traditional Chinese medicine (TCM), particularly by inhibiting FTO functions. Molecular docking was performed to screen TCM compounds from TCM Database@Taiwan (http://tcm.cmu.edu.tw). Three candidates were identified that contained either a tetrahydropyridine group or potent electronegative phenol group in the structure scaffold. Molecular dynamics simulation analysis of the docking poses of each complex indicated stabilizing trends in the protein-ligand complex movements. In addition, the number of hydrogen bonds increased throughout the 20 ns simulation. These results suggest that these TCM candidates could be potential FTO inhibitors through competitive inhibition.

Neuroprotective effect of luteolin on amyloid beta protein (25-35)-induced toxicity in cultured rat cortical neurons.

The present study was carried out to investigate the neuroprotective effect of luteolin on amyloid beta (Abeta) (25-35)-induced neurotoxicity using cultured rat cortical neurons. After exposure of primary cultures of rat cortical cells to 10 muM Abeta (25-35) for 48 h, cortical cell cultures exhibited marked apoptotic death. Pretreatment with luteolin (1, 10 microM) significantly protected cortical cell cultures against Abeta (25-35)-induced toxicity. Luteolin (1, 10 microM) showed a concentration-dependent inhibition on 10 muM Abeta (25-35)-induced apoptotic neuronal death, as assessed by MTT assay. Furthermore, luteolin reduced apoptotic characteristics by DAPI staining. For Western blot analysis, the results showed that the protective effect of luteolin on Abeta (25-35)-induced neurotoxicity was mediated by preventing of ERK-p, JNK, JNK-p, P38-p and caspase 3 activations in rat primary cortical cultures. Taken together, the results suggest that luteolin prevents Abeta (25-35)-induced apoptotic neuronal death through inhibiting the protein level of JNK, ERK and p38 MAP kinases and caspase 3 activations.

Yam (Dioscorea pseudojaponica Yamamoto) ameliorates cognition deficit and attenuates oxidative damage in senescent mice induced by D-galactose.

This study attempted to access the neuroprotective effect of yam (Dioscorea pseudojaponica Yamamoto) on the senescent mice induced by D-gal. The mice in the experiments were administered orally with yam (20, 100 or 500 mg/kg for 4 weeks, from the sixth week). The learning and memory abilities of the mice in Morris water maze test and the mechanisms involved in the neuroprotective effect of yam on the mice brain tissue were investigated. The content of diosgenin in the yam was also detected by using HPLC. Mice treated with yam were found to significantly improve their learning and memory abilities in Morris water maze test compared to those treated with D-gal (200 mg/kg for 10 weeks). In addition, yam was also found to increase the activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx) and decrease the malondialdehyde (MDA) level on the brains of D-gal treated mice. Finally, the amount of diosgenin in the yam was 5.49 mg/g extract. To sum up, these results indicate that yam had the potential to be a useful treatment for cognitive impairment in TCM. Its beneficial effect may be partly mediated via enhancing endogenous antioxidant enzymatic activities.