Bow hunter's syndrome due to an anomalous right vertebral artery origin and contralateral absence: a case report and literature review.

BACKGROUND: Bow Hunter's syndrome (BHS), also known as rotational vertebral artery occlusion (RVAO), is a rare condition characterized by dynamic vertebrobasilar insufficiency due to position-dependent occlusion of the vertebral artery (VA). In the existing literature, most cases of BHS are attributed to osteophytic compression originating from the occipital condyle or within the transverse foramen, often accompanied by anatomical abnormalities of the VA. However, cases presenting solely with VA anomalies in the absence of any cervical vertebral structural abnormality are rare. This case report presents a unique instance of BHS in a 56-year-old male, attributed to the anomalous origin of the right VA and the absence of the left VA, without cervical structural abnormalities. CASE PRESENTATION: The patient exhibited symptoms like episodic dizziness and vertigo, which were exacerbated by rightward head rotation and alleviated upon returning to a neutral position. Diagnostic evaluation, including digital subtraction angiography, revealed that the right VA originated from the right common carotid artery and compression-induced stenosis of the right VA during head rotation. Conservative management, including avoidance of certain head movements and anti-arteriosclerosis medication, led to symptom resolution over a two-year follow-up period. CONCLUSIONS: This report contributes to the understanding of BHS by highlighting a rare vascular anomaly presentation and incorporates a review of 14 similar case reports in the literature describing that an anatomical abnormality of the VA is mainly responsible for the pathology of BHS in the absence of cervical vertebral anomalies, thus emphasizing the need for careful diagnostic and management strategies.

The association between polyunsaturated fatty acids and chronic obstructive pulmonary disease: a meta-analysis.

Background: Chronic obstructive pulmonary disease (COPD) is a common respiratory disease, and its development and prognosis are influenced by many nutrients. However, the relationship between polyunsaturated fatty acids (PUFAs) and COPD remains unclear. Methods: This study searched all literature reports on PUFAs and COPD based on electronic databases from their inception up to October 2023. Meta-analysis was conducted to evaluate the differences in PUFAs between COPD patients and controls, the risk of COPD in subjects with different levels of PUFA concentrations, and the effect of PUFA supplementation on COPD. Results: A total of nineteen studies met our inclusion criteria, which included 155 636 subjects. Our meta-analysis results showed that the daily dietary intake of PUFAs was lower in COPD patients than in controls (SMD = -0.80 g, 95% CI: -1.28, -0.31 g, I2 = 98.6%, P < 0.001). Meanwhile, the lower n-3 PUFA levels and higher n-6 PUFA levels were associated with an increased risk of COPD (effect size n-3 = 0.87, 95% CI: 0.77, 0.98, I2 = 52.2%, P = 0.018; effect size n-6 = 1.23, 95% CI: 1.05, 1.43, I2 = 75.2%, P < 0.001). Furthermore, the content of low-density lipoprotein cholesterol in the PUFA supplementation group was higher than that in the control group (SMD = 0.63 mg dL-1, 95% CI: 0.15, 1.12 mg dL-1, I2 = 0.0%, P = 0.697). Conclusions: Our meta-analysis indicated a potential relationship between PUFAs and COPD. More large-scale prospective cohort studies and clinical trials are necessary to validate this relationship.

Covalently Linking Reduced Graphene Oxide Facilitated Electrodeposition of MoS2 on Silicon Pyramidal Photocathode To Enhance Hydrogen Evolution.

In recent years, increasing attention has been paid to photoelectrochemical (PEC) hydrogen production owing to the utilization of sustainable solar energy and its promising performance. Silicon-based composites are generally considered ideal materials for PEC hydrogen production. However, slow reaction kinetics and poor stability are still key factors hindering the development of silicon-based photoelectrocatalysts. Herein, we present an n+-p Si pyramidal photocathode assembly method to load reduced graphene oxide (rGO) onto the surface of the n+-p Si pyramid by covalently linking (Si/rGO). rGO is utilized as a conductive layer to reduce the interfacial charge-transfer resistance. Then, MoS2 can be successfully electrodeposited on the surface of Si/rGO to form the Si/rGO/MoS2 composite, which possesses excellent PEC hydrogen evolution performance with a high and stable photocurrent of -41.6 mA cm-2 and a hydrogen evolution rate of about 18.1 µmol min-1 cm-2 under 0 V (vs RHE). The covalently linking rGO layer effectively enhances the transfer of photogenerated carriers between the Si substrate and MoS2. MoS2 provides abundant hydrogen evolution active sites, which accelerate the surface reaction kinetics, as well as a protective layer for the Si pyramidal array structure. This work provides a low-cost, convenient, and efficient way of preparing silicon-based photocathodes.

Metastasis-associated 1 localizes to the sarcomeric Z-disc and is implicated in skeletal muscle pathology.

Metastasis-associated 1 (MTA1), a subunit of the nucleosome remodeling and histone deacetylation (NuRD) corepressor complex, was reported to be expressed in the cytoplasm of skeletal muscles. However, the exact subcellular localization and the functional implications of MTA1 in skeletal muscles have not been examined. This study aims to demonstrate the subcellular localization of MTA1 in skeletal muscles and reveal its possible roles in skeletal muscle pathogenesis. Striated muscles (skeletal and cardiac) from C57BL/6 mice of 4-5 weeks were collected to examine the expression of MTA1 by Western blotting and immunohistochemistry. Immunofluorescence and immunoelectron microscopy were performed for MTA1, α-actinin (a Z-disc marker protein), and SMN (survival of motor neuron) proteins. Gene Expression Omnibus (GEO) data sets were analyzed using the GEO2R online tool to explore the functional implications of MTA1 in skeletal muscles. MTA1 expression was detected by Western blotting and immunohistochemistry in skeletal and cardiac muscles. Subcellular localization of MTA1 was found in the Z-disc of sarcomeres, where α-actinin and SMN were expressed. Data mining of GEO profiles suggested that MTA1 dysregulation is associated with multiple skeletal muscle defects, such as Duchenne muscular dystrophy, Emery-Dreifuss muscular dystrophy, nemaline myopathy, and dermatomyositis. The GEO analysis also showed that MTA1 expression gradually decreased with age in mouse skeletal muscle precursor cells. The subcellular localization of MTA1 in sarcomeres of skeletal muscles implies its biological roles in sarcomere structures and its possible contribution to skeletal muscle pathology.

Two-way rushing travel: Cathodic-anodic coupling of Bi2O3-SnO@CuO nanowires, a bifunctional catalyst with excellent CO2RR and MOR performance for the efficient production of formate.

Electrocatalytic carbon dioxide reduction reaction (CO2RR) generates high value-added products and simultaneously reduces excess atmospheric CO2 concentrations, is regarded as a potential approach to achieve carbon neutrality. However, the kinetic process of the anode oxygen evolution reaction (OER) is slow, resulting in a poor electrochemical efficiency of CO2RR. It is a breakthrough to replace OER with methanol oxidation reaction (MOR), which has more advantageous reaction kinetics. Herein, this work proposed a bifunctional catalyst Bi2O3-SnO modified CuO nanowires (Bi2O3-SnO@CuO NWs) with excellent CO2RR and MOR performance. For CO2RR, Bi2O3-SnO@CuO NWs achieved more than 90% formate selectivity at wide potential windows from -0.88 to -1.08 V (vs. reversible hydrogen electrode (RHE)), peaking at 96.6%. Meanwhile, anodic Bi2O3-SnO@CuO NWs achieved 100 mA cm-2 at a low potential of 1.53 V (vs. RHE), possessing nearly 100% formate selectivity ranging from 1.6 to 1.8 V (vs. RHE). Impressively, by coupling cathodic CO2RR and anodic MOR, the integrated electrolytic cell realized co-production of formate (cathode: 94.7% and anode: 97.5%), minimizing the energy input by approximately 69%, compared with CO2RR. This work provided a meaningful perspective for the design of bifunctional catalysts and coupling reaction systems in CO2RR.

CT-based three-dimensional invasiveness analysis of adenocarcinoma presenting as pure ground-glass nodules.

Background: We invest computed tomography (CT) image differences between non-invasive adenocarcinomas (NIAs) and invasive adenocarcinomas (IAs) presenting as pure ground glass nodules (GGNs). Methods: From 2013 to 2019, 48 pure GGNs were surgically resected in 45 patients. Of these, 40 were pathologically diagnosed as non-small cell lung cancers (NSCLCs). We assessed them using the Synapse Vincent (Fujifilm Co., Ltd., Tokyo, Japan) three-dimensional (3D) analysis system; we drew histograms of the CT densities. We calculated the maximum, minimum, means, and standard deviations of the densities. The proportions of GGNs of high CT density were compared between the two groups. The diagnostic performance was investigated via receiver operating curve (ROC) analysis. Results: Of the 40 pure GGNs, 20 were NIAs (4 adenocarcinomas in situ and 16 minimally IAs) and 20 IAs. Significant correlations were evident between histological invasiveness and the maximum and mean CT densities and the standard deviation. Neither the nodule volume nor the minimum CT density significantly predicted invasiveness. A CT volume density proportion >-300 Hounsfield units optimally predicted the invasiveness of pure GGNs; the cutoff was 5.41% with a sensitivity of 85% and a specificity of 95%. Conclusions: CT density reflected the invasiveness of pure GGNs. A CT volume proportion density >-300 Hounsfield units may significantly predict histological invasiveness.

Changes in Microeukaryotic Communities in the Grand Canal of China in Response to Floods.

Floods are frequent natural disasters and could have serious impacts on aquatic environments. Eukaryotic communities in artificial canals influenced by floods remain largely unexplored. This study investigated the spatiotemporal variabilities among eukaryotes in response to floods in the Grand Canal, China. Generally, 781,078 sequence reads were obtained from 18S rRNA gene sequencing, with 304,721 and 476,357 sequence reads detected before and after flooding, respectively. Sediment samples collected after the floods exhibited a higher degree of richness and biodiversity but lower evenness than those before the floods. The eukaryotic communities changed from Fungi-dominated before floods to Stramenopile-dominated after floods. The spatial turnover of various species was the main contributor to the longitudinal construction of eukaryotes both before the floods (ßSIM = 0.7054) and after the floods (ßSIM = 0.6858). Some eukaryotic groups responded strongly to floods and might pose unpredictable risks to human health and environmental health. For example, Pezizomycetes, Catenulida, Glomeromycetes, Ellipura, etc. disappeared after the floods. Conversely, Lepocinclis, Synurale, Hibberdiales, Acineta, Diptera, and Rhinosporidium were all frequently detected after the floods, but not prior to the floods. Functional analyses revealed amino acid metabolism, carbohydrate metabolism, translation, and energy metabolism as the main metabolic pathways, predicting great potential for these processes in the Grand Canal.

Cerebral edema after ischemic stroke: Pathophysiology and underlying mechanisms.

Ischemic stroke is associated with increasing morbidity and has become the main cause of death and disability worldwide. Cerebral edema is a serious complication arising from ischemic stroke. It causes an increase in intracranial pressure, rapid deterioration of neurological symptoms, and formation of cerebral hernia, and is an important risk factor for adverse outcomes after stroke. To date, the detailed mechanism of cerebral edema after stroke remains unclear. This limits advances in prevention and treatment strategies as well as drug development. This review discusses the classification and pathological characteristics of cerebral edema, the possible relationship of the development of cerebral edema after ischemic stroke with aquaporin 4, the SUR1-TRPM4 channel, matrix metalloproteinase 9, microRNA, cerebral venous reflux, inflammatory reactions, and cerebral ischemia/reperfusion injury. It also summarizes research on new therapeutic drugs for post-stroke cerebral edema. Thus, this review provides a reference for further studies and for clinical treatment of cerebral edema after ischemic stroke.

Feasibility of electromagnetic navigation bronchoscopy-guided lung resection for pulmonary ground-glass opacity nodules.

BACKGROUND: Recent advances in imaging modalities and recommended low-dose computed tomography screening programs have made it easier to diagnose early lung cancer. However, the diagnosis of small ground-glass nodules (GGNs) has been problematic due to inappropriate specimen procurement and failure of conventional percutaneous core needle biopsy. Thus, we aimed to evaluate the usefulness of electromagnetic navigation bronchoscopy (ENB)-guided video-assisted lung resection for not only the diagnosis but also treatment of GGNs. METHODS: From 2017 to 2019, 110 patients with suspicious lung cancer lesions that were not diagnosed by conventional procedure underwent ENB-guided lung resection. Among 35 cases of GGNs, 33 cases of localization were included in this study (two cup biopsy cases were excluded). We used SuperDimension™ for the ENB procedure. After general anesthesia, indigo carmine (0.3-0.5 mL) was injected, and GGNs were resected through video-assisted thoracoscopic surgery. RESULTS: Of the 33 GGNs, 16 were pure (2 adenocarcinomas in situ, 5 minimally invasive adenocarcinomas (MIAs), 3 adenocarcinomas, and 6 benign lesions) and 17 were mixed (1 MIA, 11 adenocarcinomas, and 5 benign lesions). The mean size of all lesions was 11.2±7.78 mm, mean distance to the pleura was 11.2±14.2 mm, and mean ENB procedure time was 18.8±8.88 minutes. Dye localization and surgical resection of GGN were successful in all cases. There was no procedure-related complication. CONCLUSIONS: ENB is a feasible and highly accurate localization method for minimally invasive lung resection of small GGNs.

Enhanced alcohol degradation and hepatic protective effects of an Acetobacter Pasteurianus-derived product, CureZyme-ACE, in an acute intoxication rat model.

Excessive alcohol consumption induces acute intoxication and various hepatic diseases. In this study, we investigated the effect of the CureZyme-ACE (CA), Acetobacter Pasteurianus (AP)-derived product, in acute intoxication rats. The ethanol and acetaldehyde levels of serum were lower in rats treated with CA than those who only treated ethanol. The activities of alcohol dehydrogenase and acetaldehyde dehydrogenase also recovered faster in the CA group than only-ethanol group. The transaminase levels (AST, ALT) in the CA group were significantly lower than only-ethanol group. In addition, Hepatic histological analyses and stomach wall were demonstrated that the CA-treated group recovered faster than only-ethanol group. With regard to most characteristics, we found that CA had dose-dependent effects. At high concentrations of CA, there were no differences in the tested parameters compared to those of normal rats. These findings indicate that CA reduces the serum alcohol concentration and some of the hepatic damage caused by alcohol intoxication.

Lysinimonas yzui sp. nov., isolated from cattail root soil from mine tailings.

A yellow-pigmented, Gram-stain-negative, aerobic, non-motile rod shaped, mesophilic bacterium, designated strain N7XX-4T, was isolated from cattail root grown on the mine tailings of Phoenix mountain, Tongling city, Anhui Province (PR China). Analysis of the 16S rRNA gene sequence revealed that the strain represented a novel member of the family Microbacteriaceae. The nearest phylogenetic neighbour was Lysinimonas kribbensis MSL-13T (97.8 % 16S rRNA gene sequence similarity). The most abundant fatty acid in whole cells of N7XX-4T was anteiso-C15 : 0 (29.9 %). The predominant menaquinones were MK-12(H2), MK-13(H2) and MK-11(H2). The peptidoglycan type of the isolate was B1δ with l-Lys as the diagnostic cell-wall diamino acid. On the basis of differences in phenotypic and genotypic characteristics, strain N7XX-4T (=CGMCC 1.16548T=DSM 106791T=JCM 32630T) is designated as the type strain of a novel species of the genus Lysinimonas, for which the name Lysinimonas yzui sp. nov. is proposed.

Differential expression of serum proteins in multiple myeloma.

The exact cause instigating multiple myeloma (MM) has not been fully elucidated, and the disease has a median survival of 6 months without any treatment. To identify potential biomarkers of MM, serum proteins reflecting alteration in their proteomes were analyzed in 6 patients with MM compared with 6 healthy controls using two-dimensional electrophoresis (2-DE) and matrix-assisted laser desorption/ionization time-of flight mass spectrometry. The most notable differentially expressed proteins were validated by immunoblotting and changes in mRNA expression were evaluated by reverse transcription-quantitative polymerase chain reaction (RT-qPCR). A total of 11 differentially expressed protein spots were found. The expression levels of 7 proteins [Immunoglobulin heavy constant µ; proto-oncogene diffuse B-cell lymphoma (DBL2); 26S protease regulatory subunit 4 (P26s4); serum albumin; haptoglobin; and two unknown proteins with isoelectronic point (pI) of 6.41 and molecular weight of 35.4 kDa, and pI of 8.05 and molecular weight of 27.4 kDa, respectively] were downregulated in MM compared with healthy controls. Expression of gel actin-related protein 2/3 complex subunit 1A (ARPC1A); immunoglobulin heavy constant γ 1; fibrinogen α chain (FGA) fragment D; and zinc finger protein 70 were increased in serum of MM patients. Protein expressions of ARPC1A, FGA, P26s4 and DBL2 were measured by immunoblotting in an independent cohort of 12 MM patients and 10 healthy controls. RT-qPCR analysis demonstrated that ARPC1A expression only mimicked protein expression, whereas FGA, PSMC1 (encoding P26s4) and MCF2 (encoding DBL2) did not exhibit significant changes in mRNA expression between control and MM samples. These proteins represent putative serological biomarkers for patients with MM.

Antiobesity Effects of Short-Chain Chitosan in Diet-Induced Obese Mice.

Dietary chitosan is known for its antiobesity effects by combining with bile acid and lipid droplets. When the chitosan structure is broken into short chains, the fat-binding capacity increases. The aim of this study was to compare long-chain chitosan (LC) with short-chain chitosan (SC) for their antiobesity effects in high-fat diet (HFD)-induced obese C57BL/6J mice for 12 weeks. The body weights of mice in both chitosan groups were decreased, especially in the SC group compared with the LC group. Total white adipose tissue and visceral fat weights were also decreased in mice of the SC group more than those of the HFD group. Moreover, SC supplementation lowered plasma triglyceride (TG) and cholesterol levels, whereas LC only lowered plasma free fatty acid level. Fecal lipids were increased in mice of both LC and SC groups, and hepatic TG and cholesterol levels were decreased in both groups. SC lowered phosphatidate phosphohydrolase activity and elevated ß-oxidation in the liver. Furthermore, SC decreased the expression of the hepatic lipid-regulating genes, including fatty acid synthase, peroxisome proliferator-activated receptor (PPAR)γ1, and PPARγ2; and increased the expression of carnitine palmitoyl transferase 1α and peroxisome proliferator-activated receptor γ coactivator (PGC)1α genes. In conclusion, we demonstrated that long-term supplementation of SC can ameliorate body weight and lipid levels by increasing lipid excretion and regulating lipid metabolism, including some enzyme activities and gene expression levels, in HFD-induced obese mice.

A rare case of intracranial teratocarcinosarcoma: Case report and review of literature.

BACKGROUND: Teratocarcinosarcoma (TCS) is a rare malignant neoplasm with epithelial and mesenchymal components such as fibroblasts, cartilage, bone and smooth muscle. With less than 100 total reported cases, this malignant neoplasm is rarely encountered by neurosurgeons because it primarily involves the nasal cavity and paranasal sinuses. CASE DESCRIPTION: A 55-year-old male with chronic frontal headaches was found to have a frontal mass with involvement of nasal sinus and right ethmoid sinus. The patient underwent preoperative embolization of tumor followed by bilateral frontal craniotomy for near total resection of the tumor. Patient did well postoperatively without new neurological deficits. CONCLUSION: Although cases with intracranial involvement are scarce, treatment with surgical resection with or without adjuvant treatments of chemotherapy and radiation therapy is the most widely accepted with goal for gross total resection. In our case, we achieved near total resection and the patient continues to do well without any gross neurological deficits.

ß-elemene enhances anticancer bone neoplasms efficacy of paclitaxel through regulation of GPR124 in bone neoplasms cells.

The purpose of the present study was to investigate the anticancer effects of ß-elemene and paclitaxel for bone neoplasms. MTT assay, reverse transcription-quantitative polymerase chain reaction, western blotting, flow cytometry and immunostaining were used to analyze the combined effects of ß-elemene and paclitaxel both in vitro and in vivo. The results demonstrated that combined treatment of ß-elemene and paclitaxel (ß-elemene-paclitaxel) significantly inhibited growth and aggressiveness of U-2OS cells compared with either ß-elemene or paclitaxel treatment alone. It was demonstrated that ß-elemene promoted paclitaxel-induced apoptosis of U-2OS cells. Anti-apoptosis B-cell lymphoma (Bcl)-2 and Bcl-w genes were downregulated and pro-apoptotic Bcl-2-associated agonist of cell death and caspase-3 genes were upregulated in U-2OS cells following treatment with ß-elemene-paclitaxel. Treatment of ß-elemene-paclitaxel arrested the cell cycle and decreased cyclin-dependent kinase, cyclin-B1, P21 and P27 expression levels and decreased resistant genes alterations of ATP binding cassette subfamily B member 1, LDL receptor related protein and TS in U-2OS cells. Results demonstrated that ß-elemene-paclitaxel decreased G-protein coupled receptor 124 (GPR124), vascular endothelial growth factor receptor, matrix metallopeptidase (MMP)-3, MMP-9 expression levels and increased endostatin, TIMP metallopeptidase inhibitor (TIMP)-1, TIMP-2 expression in U-2OS cells. In vivo assay demonstrated that ß-elemene-paclitaxel treatment inhibited tumor growth of BALB/c-nu/nu nude mice and prolonged survival rate of tumor-bearing mice. Immunostaining demonstrated that ß-elemene-paclitaxel treatment increased apoptotic bodies, GPR124 and increased endostatin, TIMP-1 and TIMP-2 expression in tumor tissues. In conclusion, these results suggest that the combined treatment of ß-elemene-paclitaxel is more effective at inhibiting bone neoplasm growth than ß-elemene or paclitaxel single treatment GPR124.

Dendropanax morbifera Prevents Cardiomyocyte Hypertrophy by Inhibiting the Sp1/GATA4 Pathway.

An extract of Dendropanax morbifera branch exerts antioxidant, anti-inflammatory, antithrombotic, and anticancer activities. The purpose of this study was to investigate the effect of the extract in isoproterenol-induced cardiac hypertrophy. Phalloidin staining showed that treatment with the extract dramatically prevents isoproterenol-induced H9c2 cell enlargement and the expression of cardiac hypertrophic marker genes, including atrial natriuretic peptide (ANP) and B-type brain natriuretic peptide (BNP). Further, pretreatment with the extract decreased isoproterenol-induced GATA4 and Sp1 expression in H9c2 cells. Overexpression of Sp1 induced the expression of GATA4. The forced expression of Sp1 or its downstream target GATA4, as well as the co-transfection of Sp1 and GATA4 increased the expression of ANP, which was decreased by treatment with the extract. To further elucidate the regulation of the Sp1/GATA4-mediated expression of ANP, knockdown experiments were performed. Transfection with small interfering RNAs (siRNAs) for Sp1 or GATA4 decreased ANP expression. The extract did not further inhibit the expression of ANP reduced by the transfection of GATA4 siRNA. Sp1 knockdown did not affect the expression of ANP that was induced by the overexpression of GATA4; however, GATA4 knockdown abolished the expression of ANP that had been induced by Sp1 overexpression. The extract treatment also attenuated the isoproterenol-induced activation of p38 MAPK, ERK1/2, and JNK1. Hesperidin, catechin, 2,5-dihydroxybenzoic acid, and salicylic acid are the main phenolic compounds present in the extract as observed by high performance liquid chromatography. Hesperidin and 2,5-dihydroxybenzoic acid attenuated isoproterenol-induced cardiac hypertrophy. These findings suggest that the D. morbifera branch extract prevents cardiac hypertrophy by downregulating the activation of Sp1/GATA4 and MAPK signaling pathways.

Gallic acid improves cardiac dysfunction and fibrosis in pressure overload-induced heart failure.

Gallic acid is a trihydroxybenzoic acid found in tea leaves and some plants. Here, we report the effect of gallic acid on cardiac dysfunction and fibrosis in a mouse model of pressure overload-induced heart failure and in primary rat cardiac fibroblasts, and compare the effects of gallic acid with those of drugs used in clinics. Gallic acid reduces cardiac hypertrophy, dysfunction, and fibrosis induced by transverse aortic constriction (TAC) stimuli in vivo and transforming growth factor ß1 (TGF-ß1) in vitro. It decreases left ventricular end-diastolic and end-systolic diameter, and recovers the reduced fractional shortening in TAC. In addition, it suppresses the expression of atrial natriuretic peptide, brain natriuretic peptide, skeletal α-actin, and ß-myosin heavy chain. Administration of gallic acid decreases perivascular fibrosis, as determined by Trichrome II Blue staining, and reduces the expression of collagen type I and connective tissue growth factor. However, administration of losartan, carvedilol, and furosemide does not reduce cardiac dysfunction and fibrosis in TAC. Moreover, treatment with gallic acid inhibits fibrosis-related genes and deposition of collagen type I in TGF-ß1-treated cardiac fibroblasts. These results suggest that gallic acid is a therapeutic agent for cardiac dysfunction and fibrosis in chronic heart failure.

Gallic acid attenuates calcium calmodulin-dependent kinase II-induced apoptosis in spontaneously hypertensive rats.

Hypertension causes cardiac hypertrophy and leads to heart failure. Apoptotic cells are common in hypertensive hearts. Ca2+ /calmodulin-dependent protein kinase II (CaMKII) is associated with apoptosis. We recently demonstrated that gallic acid reduces nitric oxide synthase inhibition-induced hypertension. Gallic acid is a trihydroxybenzoic acid and has been shown to have beneficial effects, such as anti-cancer, anti-calcification and anti-oxidant activity. The purpose of this study was to determine whether gallic acid regulates cardiac hypertrophy and apoptosis in essential hypertension. Gallic acid significantly lowered systolic and diastolic blood pressure in spontaneously hypertensive rats (SHRs). Wheat germ agglutinin (WGA) and H&E staining revealed that gallic acid reduced cardiac enlargement in SHRs. Gallic acid treatment decreased cardiac hypertrophy marker genes, including atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP), in SHRs. The four isoforms, α, ß, δ and γ, of CaMKII were increased in SHRs and were significantly reduced by gallic acid administration. Gallic acid reduced cleaved caspase-3 protein as well as bax, p53 and p300 mRNA levels in SHRs. CaMKII δ overexpression induced bax and p53 expression, which was attenuated by gallic acid treatment in H9c2 cells. Gallic acid treatment reduced DNA fragmentation and the TUNEL positive cells induced by angiotensin II. Taken together, gallic acid could be a novel therapeutic for the treatment of hypertension through suppression of CaMKII δ-induced apoptosis.

Gallic Acid Reduces Blood Pressure and Attenuates Oxidative Stress and Cardiac Hypertrophy in Spontaneously Hypertensive Rats.

Gallic acid (GA) has been reported to have beneficial effects on cancer, vascular calcification, and diabetes-induced myocardial dysfunction. We hypothesized that GA controls hypertension via oxidative stress response regulation in an animal model for essential hypertension. Spontaneously hypertensive rats (SHRs) were administered GA for 16 weeks. GA treatment lowered elevated systolic blood pressure in SHRs through the inhibition of vascular contractility and components of the renin-angiotensin II system. In addition, GA administration reduced aortic wall thickness and body weight in SHRs. In SHRs, GA attenuated left ventricular hypertrophy and reduced the expression of cardiac-specific transcription factors. NADPH oxidase 2 (Nox2) and GATA4 mRNA expression was induced in SHR hearts and angiotensin II-treated H9c2 cells; this expression was downregulated by GA treatment. Nox2 promoter activity was increased by the synergistic action of GATA4 and Nkx2-5. GA seems to regulate oxidative stress by inhibiting the DNA binding activity of GATA4 in the rat Nox2 promoter. GA reduced the GATA4-induced Nox activity in SHRs and angiotensin II-treated H9c2 cells. GA administration reduced the elevation of malondialdehyde levels in heart tissue obtained from SHRs. These findings suggest that GA is a potential therapeutic agent for treating cardiac hypertrophy and oxidative stress in SHRs.

Gallic acid attenuates pulmonary fibrosis in a mouse model of transverse aortic contraction-induced heart failure.

Gallic acid, a trihydroxybenzoic acid found in tea and other plants, attenuates cardiac hypertrophy, fibrosis, and hypertension in animal models. However, the role of gallic acid in heart failure remains unknown. In this study, we show that gallic acid administration prevents heart failure-induced pulmonary fibrosis. Heart failure induced in mice, 8weeks after transverse aortic constriction (TAC) surgery, was confirmed by echocardiography. Treatment for 2weeks with gallic acid but not furosemide prevented cardiac dysfunction in mice. Gallic acid significantly inhibited TAC-induced pathological changes in the lungs, such as increased lung mass, pulmonary fibrosis, and damaged alveolar morphology. It also decreased the expression of fibrosis-related genes, including collagen types I and III, fibronectin, connective tissue growth factor (CTGF), and phosphorylated Smad3. Further, it inhibited the expression of epithelial-mesenchymal transition (EMT)-related genes, such as N-cadherin, vimentin, E-cadherin, SNAI1, and TWIST1. We suggest that gallic acid has therapeutic potential for the treatment of heart failure-induced pulmonary fibrosis.