XCHT alleviates the pancreatic fibrosis via VDR/NLRP3 signaling pathway in a mouse model of CP.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiao Chai Hu Tang (XCHT) derived from the classic medical book Shang Han Lun (Treatise on Febrile Diseases) in the Eastern Han Dynasty, which has been widely used in China and other Asian countries for the treatment of inflammation and fibrosis of chronic pancreatitis (CP), but the therapeutic mechanism of XCHT in pancreatic fibrosis remains unclear. AIM OF THE STUDY: This study aimed to evaluate the intervention effects and explore pharmacological mechanism of XCHT on inflammation and fibrosis in cerulein-induced CP model. MATERIALS AND METHODS: Fifty male C57BL/6 mice were randomly divided into five main groups, 10 animals in each: Control, CP model (50 µg/kg cerulein), high dose XCHT-treated CP group (60 g/kg XCHT), medium dose XCHT-treated CP group (30 g/kg XCHT) and low dose XCHT-treated CP group (15 g/kg XCHT). Different doses of XCHT were given to mice by gavage twice a day for 2 weeks after the CP model induction. Pancreatic tissues were harvested and the pancreatic inflammation and fibrosis were evaluated by histological score, Sirius red staining, and alpha-smooth muscle actin (α-SMA) immunohistochemical staining. ELISA, IHC and RT-qPCR were performed to detect the expression of Vitamin D3 (VD3) and Vitamin D receptor (VDR) in serum and pancreatic tissues, respectively. The expressions of NLRP3 inflammasome related genes and molecules were assayed by WB, IHC and RT-qPCR. RESULTS: The pathohistological results demonstrated that XCHT markedly inhibited the fibrosis and chronic inflammation of cerulein-induced CP, indicated by reduction of collagen I, collagen III, α-SMA, and NLRP3 expressions. XCHT significantly increased VD3 and VDR expression while reduced the pancreatic NLRP3 expression. Correspondingly, XCHT decreased the levels of NLRP3 downstream targets IL-1ß, TNF-α and IL-6. CONCLUSIONS: These results revealed that XCHT suppressed the pancreatic fibrosis and chronic inflammation in cerulein-induced CP model by enhancing the VD3/VDR expression and inhibiting the secretion of NLRP3-assoicated inflammatory factors.

Effect of tai-ji practice on the health of the elderly / Efeito da prática de tai-ji sobre a saúde dos idosos / Efecto de la práctica de tai-ji en la salud de las personas mayores

ABSTRACT Introduction: The practice of Tai-ji has shown a positive effect on the physical functions of the elderly and has been promoted as a recommended daily activity for middle-aged and elderly individuals. However, there is still no scientific evidence about its cardiorespiratory benefits. Objective: Study the effect of Tai-ji on the cardiorespiratory function and physical fitness of the elderly. Methods: A group of elderly people from the same community and in good health, considered suitable for sports experiments was divided into the experimental group for Tai-ji exercise and the control group for vigorous walking exercise. Each week, the Tai-ji exercise with eight steps and the vigorous walking exercise was performed three times in each group. Results: After six weeks of Tai-ji exercise with eight steps of five methods, the vital capacity, maximal oxygen consumption, maximal voluntary ventilation, and oxygen pulse of the experimental group were significantly increased, and the systolic and diastolic pressures were significantly reduced, evidencing an improvement in the performance of the cardiopulmonary function. Conclusion: Tai-ji exercise is beneficial for the cardiopulmonary function and physical health of the elderly and is scientifically useful for improving the mental health level and quality of life of the elderly. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.

RESUMO Introdução: A prática do Tai-ji tem demonstrado um efeito positivo nas funções físicas dos idosos, tendo sido promovida como atividade diária recomendada aos indivíduos de meia-idade e idosos. Porém ainda não há evidências científicas sobre seus benefícios cardiorrespiratórios. Objetivo: Estudar o efeito do Tai-ji sobre a função cardiorrespiratória e a aptidão física do idoso. Métodos: Um grupo de idosos da mesma comunidade e boa saúde, considerados adequados para os experimentos esportivos foi dividido em grupo experimental para o exercício de Tai-ji e no grupo de controle para o exercício de caminhada vigorosa. A cada semana, o exercício de Tai-ji com oito etapas e o vigoroso exercício de caminhada foram realizados três vezes em cada grupo. Resultados: Após seis semanas de exercício Tai-ji com oito etapas do método de cinco, a capacidade vital, o consumo máximo de oxigênio, a ventilação voluntária máxima e o pulso de oxigênio do grupo experimental foram significativamente aumentados, e as pressões sistólica e diastólica foram significativamente reduzidas, evidenciando uma melhora no desempenho da função cardiopulmonar. Conclusão: O exercício de Tai-ji é benéfico para a função cardiopulmonar e a saúde física dos idosos, mostrando-se cientificamente útil para melhorar o nível de saúde mental e a qualidade de vida dos idosos. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.

RESUMEN Introducción: La práctica del Tai-ji ha demostrado un efecto positivo en las funciones físicas de las personas mayores, habiéndose promovido como actividad diaria recomendada a los individuos de mediana y avanzada edad. Sin embargo, aún no existen pruebas científicas sobre sus beneficios cardiorrespiratorios. Objetivo: Estudiar el efecto del Tai-ji sobre la función cardiorrespiratoria y la forma física de los ancianos. Métodos: Un grupo de ancianos de la misma comunidad y en buen estado de salud, considerados aptos para experimentos deportivos, se dividió en el grupo experimental para el ejercicio Tai-ji y el grupo de control para el ejercicio de caminata vigorosa. Cada semana, se realizaron ejercicios de Tai-ji con ocho pasos y ejercicios de caminata vigorosa tres veces en cada grupo. Resultados: Después de seis semanas de ejercicio Tai-ji con ocho pasos de cinco métodos, la capacidad vital, el consumo máximo de oxígeno, la ventilación voluntaria máxima y el pulso de oxígeno del grupo experimental aumentaron significativamente, y las presiones sistólica y diastólica se redujeron significativamente, lo que evidencia una mejora en el rendimiento de la función cardiopulmonar. Conclusión: El ejercicio Tai-ji es beneficioso para la función cardiopulmonar y la salud física de los ancianos, y está científicamente demostrado que mejora el nivel de salud mental y la calidad de vida de los ancianos. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

Spinacetin alleviates doxorubicin-induced cardiotoxicity by initiating protective autophagy through SIRT3/AMPK/mTOR pathways.

BACKGROUND: Doxorubicin-induced myocardiopathy is a massive obstacle in administering chemotherapeutic drugs in cancer patients. PURPOSES: In the present study, we aim to investigate the effects of spinacetin, a flavonoid glycoside, on doxorubicin-induced cardiotoxicity. STUDY DESIGN: The doxorubicin-induced cardiotoxicity mice model was established to evaluate the cardioprotective effects of SP. The H9C2 cell line was used to study SP's potential mechanisms of action. Dexrazoxane (180 mg/kg) was used as the positive control. METHODS: The CCK-8 cell proliferation assay, hematoxylin and eosin (HE) staining, detection of serum biomarkers, flow cytometry for apoptosis, dansylcadaverine (MDC) staining, and Western blot for crucial molecules were conducted in the present study. RESULTS: SP significantly increased the survival rate of primary cardiomyocytes and decreased the serum LDH, CK-MB, TrT, and myocardial MDA level. The apoptosis of cardiomyocytes significantly decreased by SP, with upregulation of autophagy. In the H9C2 cell line, SP protects the cells from doxorubicin-induced cytotoxicity, decreases apoptosis, and increases autophagy. The subsequent mechanism study showed that the activation of AMPK/mTOR signaling was involved in the protective effects of SP on doxorubicin-induced cardiotoxicity through upregulating the expression level of SIRT3. CONCLUSION: We concluded that SP could protect against doxorubicin-induced cardiotoxicity both in vitro and in vivo by initiating protective autophagy through SIRT3/AMPK/mTOR pathways, which has not been reported previously. SP could be treated as a potential candidate for cardioprotective usage during chemotherapy. The further clinical study is still urgently needed to investigate the safety and effectiveness of SP in patients.

Psidium guajava Flavonoids Prevent NLRP3 Inflammasome Activation and Alleviate the Pancreatic Fibrosis in a Chronic Pancreatitis Mouse Model.

Chronic pancreatitis (CP) is a multifactorial, inflammatory syndrome characterized by acinar atrophy and fibrosis. Activation of NOD-like receptors family pyrin domain-containing 3 (NLRP3) inflammasome is a central mediator of multiple chronic inflammatory responses and chronic fibrosis including pancreatic fibrosis in CP. The Psidium guajavaleaf is widely used in traditional medicine for the treatment of chronic inflammation, but the anti-inflammatory effect of Psidium guajavaleaf on CP has not yet been revealed. In this study, we investigated whether the extract of total flavonoids from Psidium guajava leaves (TFPGL) plays a therapeutic mechanism on CP through NLRP3 inflammasome signaling pathway in a mouse CP model. The H&E and acid-Sirius red staining indicted that TFPGL attenuated the inflammatory cell infiltration and fibrosis significantly. The results of immunohistological staining, western blot and RT-qPCR showed that the expressions of NLRP3 and caspase-1 were significantly increased in the CP model group, while TFPGL significantly decreased the NLRP3 and caspase-1 expression at both the gene and protein levels. Moreover, ELISA assay was used to examine the levels of NLRP3 inflammasome target genes, such as caspase-1, IL-1[Formula: see text] and IL-18. We found that TFPGL treatment decreased the expression of caspase-1, IL-1[Formula: see text] and IL-18, which is critical for the NLRP3 inflammasome signaling pathway and inflammation response significantly. These results demonstrated that TFPGL attenuated pancreatic inflammation and fibrosis via preventing NLRP3 inflammasome activation and TFPGL can be used as a potential therapeutic agent for CP.

Astragalin reduces lipopolysaccharide-induced acute lung injury in rats via induction of heme oxygenase-1.

Astragalin, a bioactive component of medicinal plants such as Rosa agrestis, has anti-inflammatory and antioxidant features. Induction of heme oxygenase (HO)-1 is an effective strategy to reduce excessive generated oxidants during the pathogenesis of acute lung injury (ALI). The aim of the present study is to investigate that whether the anti-inflammatory and antioxidant features of astragalin is HO-1 dependent in lipopolysaccharide (LPS)-induced ALI. Sprague-Dawley rats were used in animal study. Intratracheal LPS was performed to induce experimental ALI model. Astragalin was administrated 1 h after LPS challenge. Human lung epithelial cells were used in cell study. Samples from rats were harvested at 24 h post LPS challenge. Astragalin treatment inhibited LPS-induced inflammatory cells infiltration in the lung and pulmonary edema. Astragalin treatment markedly enhanced the activity of HO-1 compared with vehicle-treated group at 24 h post LPS challenge. Levels of lipid hydroperoxide, a marker for oxidative stress, were decreased in astragalin-treated animals compared with vehicle-treated group. However, the protective effect of astragalin on LPS-induced ALI was abolished in an inhibitor of HO-1-treated animals. Moreover, the astragalin-induced the upregulation of HO-1 in human lung epithelial cells was inhibited when nuclear factor erythroid-2-related factor 2 (Nrf2) was silenced by small interfering RNA. Astragalin reduces LPS-induced ALI via activation of Nrf2/HO-1 pathway.

Dentoskeletal and soft tissue changes associated with miniscrew anchorage in customized lingual orthodontics.

OBJECTIVES: The goal of this study was to analyze skeletal, dental, and soft tissue changes of patients treated with customized lingual systems and to evaluate the clinical effectiveness of miniscrew anchorage. METHODS: Nine upper first premolar extraction patients who were treated with customized lingual appliances were included in this study. Miniscrews were used for reinforcement of molar anchorage. Cephalometric films and study models were obtained before treatment (T1), after alignment (T2), and after treatment (T3). Treatment effects were analyzed by cephalometric radiographs and study models. RESULTS: The upper anterior teeth were retracted significantly at T2 and T3 (4.41 ± 4.14 mm and 5.51 ± 2.48 mm, respectively). During space closure, the upper first molars showed slight mesial movement (1.50 ± 1.97 mm). The intercanine width of the upper arch increased at T2 (1.59 ± 1.81 mm), but decreased at T3 (0.11 ± 1.00 mm). The sella-nasion-A, A-nasion-B, and mandibular plane angles were not significantly changed at T3. The upper lip showed continuous retraction at both T2 and T3 (1.40 ± 1.46 mm and 2.32 ± 2.48 mm, respectively). CONCLUSIONS: By using miniscrew anchorage for lingual orthodontics, patients' dental and soft tissue changes considerably improved and molar anchorage was reinforced.

Metal-carbenicillin framework-based nanoantibiotics with enhanced penetration and highly efficient inhibition of MRSA.

The development of effective therapies to control methicillin-resistant Staphylococcus aureus (MRSA) infections is challenging because antibiotics can be degraded by the production of certain enzymes, for example, ß-lactamases. Additionally, the antibiotics themselves fail to penetrate the full depth of biofilms formed from extracellular polymers. Nanoparticle-based carriers can deliver antibiotics with better biofilm penetration, thus combating bacterial resistance. In this study, we describe a general approach for the construction of ß-lactam antibiotics and ß-lactamase inhibitors co-delivery of nanoantibiotics based on metal-carbenicillin framework-coated mesoporous silica nanoparticles (MSN) to overcome MRSA. Carbenicillin, a ß-lactam antibiotic, was used as an organic ligand that coordinates with Fe3+ to form a metal-carbenicillin framework to block the pores of the MSN. Furthermore, these ß-lactamase inhibitor-loaded nanoantibiotics were stable under physiological conditions and could synchronously release antibiotic molecules and inhibitors at the bacterial infection site to achieve a better elimination of antibiotic resistant bacterial strains and biofilms. We confirmed that these ß-lactamase inhibitor-loaded nanoantibiotics had better penetration depth into biofilms and an obvious effect on the inhibition of MRSA both in vitro and in vivo.

Molecular cloning and expression analysis of neuregulin 1 (Nrg1) in the hypothalamus of Huoyan goose during different stages of the egg-laying cycle.

Neuregulin 1 (Nrg1) is one of the most active members of the epidermal growth factor (EGF)-like family, which bind to the ErbB tyrosine kinase receptor and play many roles in modulation of synaptic activity, synaptogenesis, GABAergic neurotransmission, neurotransmitter receptor expression and the hormonal control of neuroendocrine reproductive development. In this study, we cloned and characterized the cDNA of goose Nrg1 originating from hypothalamus tissues of Huoyan goose using RACE method, investigated the mRNA expression profiles during different stages of the egg-laying cycle by real-time PCR. Multiple alignments and phylogenetic analyses of the deduced amino acid sequence were conducted using bioinformatics tools. We also determined the profiles of blood serum progesterone, estradiol, FSH and LH content during different egg-laying stages using radioimmunoassay. The cDNA of Nrg1 is consisted of 2061bp open reading frame encoding 686 amino acids. The deduced amino acid sequence of goose Nrg1 contains one EGF domain from amino acid residues 224 to 265 and shows a closer genetic relationship to the avian species than to other mammal species. The expression level of Nrg1 mRNA increased from the pre-laying period to the peak-laying period, reached its peak in the peak-laying period, and then decreased in the ceased period. The concentrations of FSH and estradiol in blood serum have the similar changing trend. These results might suggest a potential correlation between Nrg1/ErbB signaling network with the reproductive neuroendocrine of Huoyan goose.

A Case Report of Churg-Strauss Syndrome Presenting With Cardiogenic Shock Treated With Extracorporeal Membrane Oxygenation.

Churg-Strauss Syndrome (CSS) complicated with cardiogenic shock is rare. Few case reports have described successful treatment of this rare disease. However, no one has reported on the application of mechanical life support with extracorporeal membrane oxygenation (ECMO) to treat this life-threatening disease.A 36-year-old female with limb numbness for >10 days, chest tightness for 2 days, and worsening dyspnea for 5 h presented in the emergency room. Vital signs showed a low blood pressure (104/60 mm Hg), increased heart rate (158 bpm), and respiration rate (28 bpm). Laboratory tests revealed that eosinophil was significantly increased (WBC: 34.46 × 10/L, neutrophil: 7.56 × 10/L[21.9%], eosinophil: 23.84 × 10/L[69.2%]), and serum myocardial enzymes was abnormal (CK 1049U/L, CKMB-mass 145.1 µg/L, cTnI 16.24 µg/L). Myocardial injury (tachycardia with ST elevation) and poor heart function (LVEF 31%) were found by electrocardiogram and transthoracic echocardiography. On the next day, cardiogenic shock had been developed as demonstrated by deteriorating the perfusion index.Churg-Strauss Syndrome with cardiogenic shock.A series of conservative therapy with drugs such as corticosteroids, anticoagulant, antiplatelet, nitrates, calcium antagonists, inotrope, and vasopressors were initiated on the day of admission. The treatment was ineffective and a cardiogenic shock developed on the next day. Thus, ECMO was initiated immediately to stabilize circulation and perfusion. At the same time, high-dose corticosteroids combined with immunosuppressive therapy were continuously used.Symptoms of cardiogenic shock were gradually improved after ECMO treatment. Elevated values of cardiac enzymes were decreased and the dose of vasoactive drugs was reduced. Extracorporeal membrane oxygenation was discontinued after 8 days, and the patient was eventually weaned off the ventilator. The patient was discharged after 40 days treatment.Once a CSS develops into a cardiogenic shock, the ECMO should be considered as an alternative therapeutics in that it stabilizes hemodynamic status, maintains effective tissue perfusion, and provides an opportunity for the recovery of cardiac function.

Fluoride Affects Calcium Homeostasis by Regulating Parathyroid Hormone, PTH-Related Peptide, and Calcium-Sensing Receptor Expression.

Parathyroid hormone (PTH), PTH-related peptide (PTHrP), and calcium-sensing receptor (CaSR) play important roles in maintaining calcium homeostasis. Here, we study the effect of fluoride on expression of PTH, PTHrP, and CaSR both in vitro and in vivo. MC3T3-E1 cells and Sprague-Dawley rats were treated with different concentrations of fluoride. Then, the free calcium ion concentration in cell culture supernatant and serum were measured by biochemical analyzer. The expression of PTH, PTHrP, and CaSR was analyzed by qRT-PCR and Western blot. We found that the low dose of fluoride increased ionized calcium (i[Ca(2+)]) and the high dose of fluoride decreased i[Ca(2+)] in cell culture supernatant. The low dose of fluoride inhibited the PTH and PTHrP expression in MC3T3-E1 cells. The high dose of fluoride improved the PTHrP expression in MC3T3-E1 cells. Interestingly, we found that NaF decreased serum i[Ca(2+)] in rats. Fluoride increased CaSR expression at both messenger RNA (mRNA) and protein levels in MC3T3-E1 cells and rats. The expression of PTHrP protein was inhibited by fluoride in rats fed regular diet and was increased by fluoride in rats fed low-calcium diet. Fluoride also increased the expression of PTH, NF-kappaB ligand (RANKL), and osteoprotegerin (OPG) in rats. The ratio of RANKL/OPG in rats fed low-calcium food in presence or absence of fluoride was significantly increased. These results indicated that fluoride might be able to affect calcium homeostasis by regulating PTH, PTHrP, and CaSR.

Molecular cloning and expression analysis of the synaptotagmin-1 gene in the hypothalamus and pituitary of Huoyan goose during different stages of the egg-laying cycle.

BACKGROUND: Synaptotagmin-1 (Syt1) is an abundant, evolutionarily conserved integral membrane protein that plays essential roles in neurotransmitter release and hormone secretion. Neurotransmitters secreted by hypothalamic neurons can alter GnRH (gonadotropin-releasing hormones) neuronal activity by binding to and activating specific membrane receptors in pituitary cells and, in turn, control the release of gonadotropin hormones from the pituitary gland. To reveal the influence of Syt1 on the process of goose egg-laying, we cloned and characterized the cDNA of goose Syt1 originating from hypothalamus and pituitary tissues of Huoyan goose and investigated the mRNA expression profiles during different stages of the egg-laying cycle. METHODS: Hypothalamus and pituitary tissues were obtained from 36 Huoyan geese in the pre-laying period, early laying period, peak-laying period, and ceased period. The cDNA sequences of goose Syt1 were cloned and characterized from Huoyan goose tissues using 5'-RACE and 3'-RACE methods. Multiple alignments and phylogenetic analyses of the deduced Syt1 amino acid sequence were conducted using bioinformatics tools. The expression profiles of the Syt1 mRNA in the hypothalamus and pituitary during pre-laying, early laying, peak-laying and ceased period were examined using real-time PCR (qRT-PCR). RESULTS: The cDNA of Syt1 consisted of a 274 bp 5' UTR, a 1266 bp open reading frame (ORF) encoding 421 amino acids, and a 519 bp 3' UTR. The deduced amino acid sequence of goose Syt1 is highly conserved with the sequence from other species, especially with birds (more than 98%), and contains two protein kinase C2 conserved regions (C2 domain) from amino acids residue 157 to 259 and 288 to 402. The results of qRT-PCR demonstrated that the expression of Syt1 mRNA increased from the pre-laying period to the peak-laying period, reached its peak in the peak-laying period, and then decreased in the ceased period. CONCLUSIONS: To the best of our knowledge, this study is the first to obtain full-length cDNA sequences of the goose Syt1 gene, and the results of Syt1 mRNA expression profiling in the hypothalamus and pituitary tissues suggested that Syt1 may play an important role in regulating the secretion of hormones relevant to the reproduction and egg-laying of female geese.

Eyeblink conditioning in unmedicated schizophrenia patients: a positron emission tomography study.

Previous studies suggest that patients with schizophrenia exhibit dysfunctions in a widely distributed circuit-the cortico-cerebellar-thalamic-cortical circuit, or CCTCC-and that this may explain the multiple cognitive deficits observed in the disorder. This study uses positron emission tomography (PET) with O(15) H2O to measure regional cerebral blood flow (rCBF) in response to a classic test of cerebellar function, the associative learning that occurs during eyeblink conditioning, in a sample of 20 unmedicated schizophrenia patients and 20 closely matched healthy controls. The PET paradigm examined three phases of acquisition and extinction (early, middle and late). The patients displayed impaired behavioral performance during both acquisition and extinction. The imaging data indicate that, compared to the control subjects, the patients displayed decreases in rCBF in all three components of the CCTCC during both acquisition and extinction. Specifically, patients had less rCBF in the middle and medial frontal lobes, anterior cerebellar lobules I/V and VI, as well as the thalamus during acquisition and although similar areas were found in the frontal lobe, ipsilateral cerebellar lobule IX showed consistently less activity in patients during extinction. Thus this study provides additional support for the hypothesis that patients with schizophrenia have a cognitive dysmetria--an inability to smoothly coordinate many different types of mental activity--that affects even a very basic cognitive task that taps into associative learning.

High-dose glucocorticoids induce decreases calcium in hypothalamus neurons via plasma membrane Ca(2+) pumps.

In our previous studies, we occasionally found that high-dose glucocorticoids (GC) induced decrease in [Ca(2+)](i) in hypothalamus neurons. In previous articles, modulation of Ca(2+) channels by GC has been shown to contribute to the elementary regulation of several neuronal functions. However, little is known about the regulation of the Ca efflux pathways that counterbalance the Ca(2+) influx in neurons caused by high-dose GC. In this study, we demonstrate that a high-dose of GC (10 M dexamethasone) caused a 20% decrease in [Ca(2+)](i) within 2 s in cultured hypothalamic neurons; furthermore, we show that an antagonist of the GC receptor blocks this action. To ascertain the temporal sequence of relevant calcium transport mechanisms we selectively blocked the main calcium transporters, including sodium/calcium exchanger (NCX), plasma membrane calcium pumps (PMCA), and P-type Ca(2+)-ATPases of the sarcoplasmic reticulum (SERCA). The GC-induced [Ca(2+)](i) decrease disappeared completely when PMCA was blocked, but not when NCX and SERCA were blocked. These results suggest that high-dose GC (10(-6) M) rapidly decreases [Ca(2+)](i) by activating PMCA but not NCX or SERCA.