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1.
Nat Neurosci ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34795450

RESUMO

The striatum comprises multiple subdivisions and neural circuits that differentially control motor output. The islands of Calleja (IC) contain clusters of densely packed granule cells situated in the ventral striatum, predominantly in the olfactory tubercle (OT). Characterized by expression of the D3 dopamine receptor, the IC are evolutionally conserved, but have undefined functions. Here, we show that optogenetic activation of OT D3 neurons robustly initiates self-grooming in mice while suppressing other ongoing behaviors. Conversely, optogenetic inhibition of these neurons halts ongoing grooming, and genetic ablation reduces spontaneous grooming. Furthermore, OT D3 neurons show increased activity before and during grooming and influence local striatal output via synaptic connections with neighboring OT neurons (primarily spiny projection neurons), whose firing rates display grooming-related modulation. Our study uncovers a new role of the ventral striatum's IC in regulating motor output and has important implications for the neural control of grooming.

2.
Zhongguo Zhong Yao Za Zhi ; 46(16): 4131-4138, 2021 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-34467724

RESUMO

Eleven condensed tannins were isolated from the roots of Indigofera stachyodes by various column chromatography techniques including silica gel, octadecyl silica(ODS), Sephadex LH-20, and semi-preparative high performance liquid chromatography(HPLC). These compounds were identified on the basis of physicochemical properties, nuclear magnetic resonance(NMR) and mass spectrometry(MS) data as stachyotannin A(1), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4ß→8)-catechin(2), cinnamtannin D1(3), cinnamtannin B1(4), epicatechin-(2ß→O→7,4ß→8)-epiafzelechin-(4α→8)-epicatechin(5), gambiriin C(6), proanthocyanidin A1(7), proanthocyanidin A2(8), aesculitannin B(9), proanthocyanidin A4(10), and procyanidin B5(11). Compound 1 is a new compound. Compounds 2-11 were isolated from Indigofera for the first time. Furthermore, compounds 1, 2, and 4-11 showed inhibitory effects on thrombin-induced ATP release in platelets.


Assuntos
Indigofera , Proantocianidinas , Cromatografia Líquida de Alta Pressão , Espectroscopia de Ressonância Magnética , Extratos Vegetais
3.
Asian J Surg ; 2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34158200

RESUMO

BACKGROUND: Lumbar facet joint is an important element of spinal "three-joint complex". Whether there is a relationship between strange structure of facet joint and adolescent lumbar disc herniation (ALDH) is nonetheless controversial, and the current research is mainly centered on adults. OBJECTIVE: To find out the normal lumbar facet joints between 13 and 18 years old to provide anatomical basis for early diagnosis and therapy of lumbar disc herniation. METHODS: CT imaging information of 32 sufferers with lumbar disc herniation aged from 13 to 18 years old in Inner Mongolia have been collected as the ALDH group, and 62 wholesome subjects in the equal period had been chosen as the normal group. Uncooked records of continuous scanning lumbar tomography pix were imported into MIMICS 21.0 for evaluation and size in DICOM format. The parameters include facet joint height, facet joint width, et al. RESULTS: 1. The left and right transverse angle of L5S1 segment in the ALDH group were (52.41 ± 9.2) ° and (55.99 ± 10.91) ° (P < 0.05), and the differences were statistically significant. The right side is larger than the left side. 2. Facet joint thickness in L3-L5 segment of the normal group was significantly higher than that of male (1.63 ± 0.32) mm than that of female (1.38 ± 0.25) mm; In 16-18 years old group, comparison of facet joint cross-sectional area was statistically significant (22.1 ± 3.04) mm2 in male than (18.92 ± 3.71) mm2 in female. 3. In comparison between normal and ALDH group, there was significant difference in L3-4 transverse angle (P < 0.05), L4-5 facet joint height and facet joint thickness (P < 0.05), L5S1 facet joint thickness and transverse angle (P < 0.05). CONCLUSION: When ALDH occurs in the L5S1 segment, there is a substantial difference between the left and right sides of the transverse angle, and there is a difference in the thickness and the facet joint cross-sectional area between males and females, which is generally larger in males than in females. Facet joint height is larger, transverse angle of left and right is asymmetric, inferior articular process is larger, and facet joint thickness is smaller can indicate that lumbar disc herniation is effortless to occur.

4.
BMC Musculoskelet Disord ; 22(1): 498, 2021 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-34051767

RESUMO

BACKGROUND: The interference screw is the most popular device that fixes the graft for anterior cruciate ligament reconstruction, reducing the incidence of windshield effect and bungee effect. For the screw, either metallic, "bioresorbable," or polyetheretherketone (PEEK) material is available. PEEK is popular and extensively used due to its stability, biocompatibility, radiolucency, and elastic modulus. Rare relevant complications were reported, but here, we report two cases of extra-articular migrations of PEEK interference screw from the tibial tunnel after anterior cruciate reconstruction. CASE REPORT: An 18-year-old boy and a 56-year-old woman underwent anterior cruciate ligament reconstruction using a PEEK interference screw to fix the graft in the tibial tunnel. They suffered from screw extrusion from the tibial tunnel after 40 days and six months, respectively, with an incision rupture or palpable subcutaneous mass. They underwent a second operation and recovered well. CONCLUSIONS: The exact incidence of extra-articular migrations of PEEK interference screws is unknown, but it seems to be quite low; despite this and its uncertain cause, the negative effects caused by the PEEK material need to be considered.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Adolescente , Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior/cirurgia , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Parafusos Ósseos/efeitos adversos , Feminino , Humanos , Cetonas/efeitos adversos , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis
5.
BMC Anesthesiol ; 21(1): 103, 2021 04 06.
Artigo em Inglês | MEDLINE | ID: mdl-33823815

RESUMO

BACKROUND: At present, low-concentration carbohydrate is rarely used in minor trauma surgery, and its clinical efficacy is unknown. The aim of the study was to evaluate the effect of preoperative oral low-concentration carbohydrate on patient-centered quality of recovery in patients undergoing thyroidectomy using Quality of Recovery - 15 (QoR-15) questionnaire. METHODS: One hundred twenty patients were randomized to oral intake of 300 ml carbohydrate solution (CH group) or 300 ml pure water (PW group) 2 h before surgery or fasting for 8 h before surgery (F group). The QoR-15 questionnaire was administered to compare the quality of recovery at 1d before surgery (T0), 24 h, 48 h, 72 h after surgery (T1, T2, T3), and perioperative blood glucose was recorded. RESULTS: Compared to the F group, the QoR-15 scores were statistically higher in the CH and PW group at T1 (P < 0.05), and the enhancement of recovery quality reached the clinical significance at T1 in the CH group compared with the F group. Among the five dimensions of the QoR-15 questionnaire, physical comfort, physiological support and emotional dimension in the CH group were significantly better than the F group (P < 0.05) at T1. Besides, blood glucose of CH group was significantly lower than the PW group and F group at each time point after surgery. CONCLUSIONS: Low-concentration carbohydrate could decrease the incidence of postoperative hyperglycemia and improve the patient-centered quality of recovery on patients undergoing open thyroidectomy at the early stage postoperatively. TRIAL REGISTRATION: ChiCTR1900024731 . Date of registration: 25/07/2019.

6.
Minim Invasive Ther Allied Technol ; 30(4): 215-220, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32039637

RESUMO

PURPOSE: To compare the relative clinical efficacy of preoperative computed tomography (CT)-guided methylene-blue (MB) and coil localization for lung nodules (LNs). MATERIAL AND METHODS: Between January 2013 and December 2018, a total of 89 patients with LNs underwent CT-guided MB or coil localization and subsequent video-assisted thoracoscopic surgery (VATS)-guided wedge resection in our hospital. We compared the technical success of localization and wedge resection between two groups. RESULTS: In MB group, 47 LNs in 39 patients were localized, with successful localization and wedge resection rates of 97.9% and 97.9%, respectively. In the coil group, 64 LNs in 50 patients were localized, with successful localization and wedge resection rates of 96.9% and 96.9%, respectively. There were no significant differences in technical success rates of localization and wedge resection between the two groups (p = 1.000 and 1.000). The coil group sustained a longer duration between localization and VATS relative to the MB group (14.4 h vs. 1.6 h, p = .001). CONCLUSION: Both MB and coil localization were safe and effective techniques to establish a high success rate of VATS-guided wedge resection for LNs. Relative to MB localization, coil localization might be compatible with a longer delay between localization and VATS.


Assuntos
Neoplasias Pulmonares , Azul de Metileno , Humanos , Pulmão , Neoplasias Pulmonares/diagnóstico por imagem , Neoplasias Pulmonares/cirurgia , Pneumonectomia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X
8.
BMC Anesthesiol ; 20(1): 240, 2020 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-32957926

RESUMO

BACKGROUND: Opioids are the most effective antinociceptive agents, they have undesirable side effects such as respiratory depressant and postoperative nausea and vomiting. The purpose of the study was to evaluate the antinociceptive efficacy of adjuvant magnesium sulphate to reduce intraoperative and postoperative opioids requirements and their related side effects during hysteroscopy. METHODS: Seventy patients scheduled for hysteroscopy were randomly divided into 2 groups. Patients in the magnesium group (Group M) received intravenous magnesium sulfate 50 mg/kg in 100 ml of isotonic saline over 15 min before anesthesia induction and then 15 mg/kg per hour by continuous intravenous infusion. Patients in the control group (Group C) received an equal volume of isotonic saline as placebo. All patients were anesthetized under a BIS guided monitored anesthesia care with propofol and fentanyl. Intraoperative hemodynamic variables were recorded and postoperative pain scores were assessed with verbal numerical rating scale (VNRS) 1 min, 15 min, 30 min, 1 h, and 4 h after recovery of consciousness. The primary outcome of our study was total amount of intraoperative and postoperative analgesics administered. RESULTS: Postoperative serum magnesium concentrations in Group C were significantly decreased than preoperative levels (0.86 ± 0.06 to 0.80 ± 0.08 mmol/L, P = 0.001) while there was no statistical change in Group M (0.86 ± 0.07 to 0.89 ± 0.07 mmol/L, P = 0.129). Bradycardia did not occur in either group and the incidence of hypotension was comparable between the two groups. Total dose of fentanyl given to patients in Group M was less than the one administered to Group C [100 (75-150) vs 145 (75-175) µg, median (range); P < 0.001]. In addition, patients receiving magnesium displayed lower VNRS scores at 15 min, 30 min, 1 h, and 4 h postoperatively. CONCLUSIONS: In hysteroscopy, adjuvant magnesium administration is beneficial to reduce intraoperative fentanyl requirement and postoperative pain without cardiovascular side effects. Our study indicates that if surgical patients have risk factors for hypomagnesemia, assessing and correcting magnesium level will be necessary. TRIAL REGISTRATION: ChiCTR1900024596 . date of registration: July 18th 2019.


Assuntos
Analgésicos/uso terapêutico , Anestesia/métodos , Anestésicos/uso terapêutico , Histeroscopia/métodos , Sulfato de Magnésio/uso terapêutico , Dor Pós-Operatória/tratamento farmacológico , Adulto , Analgésicos Opioides/administração & dosagem , Feminino , Fentanila/administração & dosagem , Humanos
9.
Eur J Med Chem ; 201: 112510, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32592915

RESUMO

ß-Lactam, commonly referred as azetidin-2-one, is a multifunctional building block for synthesizing ß-amino ketones, γ-amino alcohols, and other compounds. Besides its well known antibiotic activity, this ring system exhibits a wide range of activities, attracting the attention of researchers. However, the structurally diverse ß-lactam analogues as anticancer agents and their different molecular targets are poorly discussed. The purpose of this review is 3-fold: (1) to explore the molecular hybridization approach to design ß-lactams hybrids as anticancer agents; (2) the structure activity relationship of the most active anticancer ß-lactams and (3) to summarize their antitumor mechanisms.


Assuntos
Antineoplásicos/farmacologia , beta-Lactamas/farmacologia , Animais , Antineoplásicos/química , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Desenho de Fármacos , Inibidores Enzimáticos/química , Inibidores Enzimáticos/farmacologia , Humanos , Estrutura Molecular , Relação Estrutura-Atividade , beta-Lactamas/química
10.
J Clin Anesth ; 62: 109742, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32088534

RESUMO

STUDY OBJECTIVES: The aim of the present study was to assess the quality of recovery from anesthesia on patients subjected to laparoscopic radical resection of colorectal cancer under epidural block combined with general anesthesia or general anesthesia by means of Quality of Recovery-15 (QoR-15) questionnaire. DESIGN: Prospective randomized trial. SETTING: The setting is at an operating room, a post-anesthesia care unit, and a hospital ward. PATIENTS: Seventy patients, aging from 65 to 79 years with an American Society of Anesthesiologists physical status II or III, were scheduled to undergo laparoscopic radical resection of colorectal cancer. INTERVENTIONS: Epidural block combined with general anesthesia or general anesthesia. MEASUREMENTS: The QoR-15 was administered by an investigator blind to group allocation before surgery (T0), at 24 and 72h after surgery (T1 and T2), and on postoperative day 7 (T3). The quality of recovery, as assessed by the score on the QoR-15, was compared between the groups. Besides, the consumption of anesthetics, respiratory recovery time, response time, extubation time, flatus time, the incidence of nausea or vomiting, the consumption of antiemetic and analgesic agents, and the duration of the hospital stay were also recorded. MAIN RESULTS: The QoR-15 scores at T1 and T2 were significantly higher in the E + G group compared with the G group (P < 0.05). Among the five dimensions of the QoR-15, physiological comfort, physiological independence, pain, and emotional dimension were significantly better at T1 in the E + G group, and physiological comfort and pain were significantly better at T2 in the E + G group. CONCLUSION: This study demonstrates that epidural block combined with general anesthesia can improve the early recovery of elderly patients after laparoscopic radical resection of colorectal cancer from the perspective of patients.


Assuntos
Neoplasias Colorretais , Laparoscopia , Idoso , Período de Recuperação da Anestesia , Anestesia Geral/efeitos adversos , Neoplasias Colorretais/cirurgia , Humanos , Estudos Prospectivos
11.
Nat Prod Res ; 34(14): 2030-2036, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30789078

RESUMO

Two new benzophenone glycosides, aquilarisides A (1) and B (2), together with six known analogues (3-8) were isolated from the pericarps of Aquilaria yunnanensis S. C. Huang. Their structures were elucidated on the basis of 1D and 2D NMR and mass spectroscopic analyses, and the absolute configuration of compound 1 was determined by experimental and calculated electronic circular dichroism (ECD) spectra. Anti-inflammatory activities of all compounds 1-8 were evaluated for their inhibitory activities against lipopolysaccharide (LPS)-stimulated induced nitric oxide (NO) production in RAW 264.7 cells using the Griess assay. Compound 2 indicated a weak inhibition of NO production.


Assuntos
Anti-Inflamatórios/isolamento & purificação , Benzofenonas/química , Glicosídeos/isolamento & purificação , Thymelaeaceae/química , Animais , Anti-Inflamatórios/química , Anti-Inflamatórios/farmacologia , Benzofenonas/isolamento & purificação , Benzofenonas/farmacologia , Glicosídeos/química , Glicosídeos/farmacologia , Lipopolissacarídeos , Espectroscopia de Ressonância Magnética , Espectrometria de Massas , Camundongos , Conformação Molecular , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Células RAW 264.7
12.
Nat Prod Res ; : 1-7, 2019 Dec 07.
Artigo em Inglês | MEDLINE | ID: mdl-31813298

RESUMO

Two new isoquinoline alkaloids (1 and 2) along with fourteen known alkaloids (3-16) were isolated from Corydalis racemosa (Thunb.) Pers. Their structures were elucidated by analyzing spectroscopic and spectrometric data (NMR, UV, IR, and MS) and comparing their spectroscopic, spectrometric and physicochemical data with the values archived in the literature. The absolute configurations of new compounds were determined via X-ray crystallographic assay and electronic circular dichroism calculations. Acetylcholinesterase (AChE) inhibitory activity of all compounds was evaluated. Compounds 5, 6, 9, 11, and 12 exhibited inhibitory activity against AChE with IC50 values ranged from 10.2 to 63.4 µM.

13.
J Neurosci ; 39(48): 9546-9559, 2019 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-31628176

RESUMO

Sensory cortices process stimuli in manners essential for perception. Very little is known regarding interactions between olfactory cortices. The piriform "primary" olfactory cortex, especially its anterior division (aPCX), extends dense association fibers into the ventral striatum's olfactory tubercle (OT), yet whether this corticostriatal pathway is capable of shaping OT activity, including odor-evoked activity, is unknown. Further unresolved is the synaptic circuitry and the spatial localization of OT-innervating PCX neurons. Here we build upon standing literature to provide some answers to these questions through studies in mice of both sexes. First, we recorded the activity of OT neurons in awake mice while optically stimulating principal neurons in the aPCX and/or their association fibers in the OT while the mice were delivered odors. This uncovered evidence that PCX input indeed influences OT unit activity. We then used patch-clamp recordings and viral tracing to determine the connectivity of aPCX neurons upon OT neurons expressing dopamine receptor types D1 or D2, two prominent cell populations in the OT. These investigations uncovered that both populations of neurons receive monosynaptic inputs from aPCX glutamatergic neurons. Interestingly, this input originates largely from the ventrocaudal aPCX. These results shed light on some of the basic physiological properties of this pathway and the cell-types involved and provide a foundation for future studies to identify, among other things, whether this pathway has implications for perception.SIGNIFICANCE STATEMENT Sensory cortices interact to process stimuli in manners considered essential for perception. Very little is known regarding interactions between olfactory cortices. The present study sheds light on some of the basic physiological properties of a particular intercortical pathway in the olfactory system and provides a foundation for future studies to identify, among other things, whether this pathway has implications for perception.


Assuntos
Ácido Glutâmico/metabolismo , Neurônios Receptores Olfatórios/metabolismo , Tubérculo Olfatório/metabolismo , Córtex Piriforme/metabolismo , Receptores de Dopamina D1/biossíntese , Receptores de Dopamina D2/biossíntese , Animais , Feminino , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Odorantes , Neurônios Receptores Olfatórios/efeitos dos fármacos , Tubérculo Olfatório/efeitos dos fármacos , Córtex Piriforme/efeitos dos fármacos , Receptores de Dopamina D1/genética , Receptores de Dopamina D2/genética , Olfato/fisiologia
14.
Medicine (Baltimore) ; 98(42): e17591, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626131

RESUMO

BACKGROUND: Spinal cord ischemia-reperfusion injury (SCII) is a common complication of spinal surgery as well as thoracic and abdominal surgery. Acute cytotoxic edema is the key pathogenic alteration. Therefore, avoiding or decreasing cellular edema has become the major target for SCII treatment. METHODS: The antiedema activity of ginsenoside Rb1 on aquaporin (AQP) 4, nerve growth factor (NGF), and brain-derived neurotrophic factor expression was detected by western blot and real-time polymerase chain reaction under conditions of oxygen-glucose deprivation/reoxygenation (OGD/R) in a rat astrocyte model in vitro. In addition, the cellular membrane permeability of AQP4 overexpressing cells or AQP4 small interfering RNA-transfected cells was detected. RESULTS: Ginsenoside Rb1 significantly prevented OGD/R-induced AQP4 downregulation in rat astrocytes. In addition, ginsenoside Rb1 treatment or AQP4 overexpression in rat astrocytes significantly attenuated the OGD/R-induced increase of cellular membrane permeability. Moreover, ginsenoside Rb1 obviously prevented the OGD/R-induced decrease of NGF and BDNT expression in rat astrocytes. CONCLUSION: These findings demonstrate that ginsenoside Rb1 can relieve spinal cord edema and improve neurological function by increasing AQP4 expression.


Assuntos
Aquaporina 4/genética , Astrócitos/metabolismo , Regulação da Expressão Gênica no Desenvolvimento , Ginsenosídeos/farmacologia , Glucose/metabolismo , Oxigênio/metabolismo , Traumatismo por Reperfusão/genética , Animais , Animais Recém-Nascidos , Aquaporina 4/biossíntese , Astrócitos/efeitos dos fármacos , Astrócitos/patologia , Western Blotting , Células Cultivadas , Modelos Animais de Doenças , Ensaio de Imunoadsorção Enzimática , RNA/genética , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/patologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medula Espinal/metabolismo , Medula Espinal/patologia
15.
Photodiagnosis Photodyn Ther ; 26: 73-78, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30836211

RESUMO

BACKGROUND: To date, it has been reported that the intrinsic factors(lesions location, lesions area, disease tynpes) and extrinsic factors(fluence rate) contribute to the pain during 5-aminolevulinic acid photodynamic therapy (ALA-PDT). But there are few studies on pain during ALA-PDT and lack of sufficient clinical evidence related to the pain intensity. OBJECTIVE: To investigate pain intensity and its relative factors during ALA-PDT and to provide clinical implication. METHODS: The pain numeric rating scale (PNRS) score was used to evaluate the patients' pain intensity at different times during ALA-PDT irradiation from 0 to 10 min during treatment. Gender, age, lesions location, lesions area, ALA concentration and fluence rate were recored. RESULTS: The trial enrolled 274 patients in total, including 118 acne patients (in face), 30 actinic keratosis(AK)patients(in face), 126 Condylomatata acuminate patients(in genitalia). The average pain score in PDT was highest in the patients with actinic keratosis(7.3 ± 0.7), and that of condylomata acuminata was the lowest (4.5 ± 1.1) (p < 0.05). The highest pain score in patients with AK, acne and condylomata acuminata was 8, 6 and 6 respectively which occurred at 4 min, 4 min and 6 min respectively. The pain score of males was higher compared with females in all of the three diseases (p < 0.05). The pain score of facial diseases (5.6 ± 1.2) was higher than that of the genitalia (4.5 ± 1.1) (p < 0.05). The lesions area was positively correlated with the pain score (p < 0.05). In facial diseases, the pain score of patients with high fluence rate (7.3 ± 0.7) was higher than patients with low fluence rate (5.1 ± 0.9) (p < 0.05). CONCLUSIONS: Intrinsic and extrinsic factors both correlate with pain during PDT. Intrinsic factors are difficult to change, so extrinsic factors are the key point to control. We can reduce the fluence rate and extend the treatment time, relieving pain intensity while still ensuring equivalent efficacy.


Assuntos
Acne Vulgar/tratamento farmacológico , Condiloma Acuminado/tratamento farmacológico , Dermatoses Faciais/tratamento farmacológico , Ceratose Actínica/tratamento farmacológico , Medição da Dor , Fotoquimioterapia/métodos , Adulto , Ácido Aminolevulínico/uso terapêutico , Dermoscopia , Feminino , Humanos , Masculino , Fármacos Fotossensibilizantes/uso terapêutico , Estudos Prospectivos
16.
Phytochemistry ; 158: 46-55, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30453219

RESUMO

Fifteen previously undescribed 2-(2-phenylethyl)chromone dimers, along with two known analogues were isolated from Chinese agarwood (Aquilaria sinensis) by a LC-MS-guided fractionation procedure. Their structures were elucidated on the basis of spectroscopic and spectrometric data (1D and 2D NMR, IR, and HRESIMS). The isolated compounds exhibited significant inhibition of nitric oxide production in lipopolysaccharide-stimulated RAW264.7 cells with IC50 values in the range 0.6-37.1 µM.


Assuntos
Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/farmacologia , Cromonas/química , Thymelaeaceae/química , Animais , Anti-Inflamatórios não Esteroides/isolamento & purificação , Cromatografia Líquida , Cromonas/isolamento & purificação , Dimerização , Avaliação Pré-Clínica de Medicamentos/métodos , Concentração Inibidora 50 , Lipopolissacarídeos/farmacologia , Espectroscopia de Ressonância Magnética , Camundongos , Estrutura Molecular , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/metabolismo , Plantas Medicinais/química , Células RAW 264.7 , Espectrometria de Massas por Ionização por Electrospray
17.
Exp Cell Res ; 374(1): 231-248, 2019 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-30513336

RESUMO

Retinal pigment epithelial cells (RPEs), a pigmented cell layer in the outer retina, are constantly exposed to photo-oxidative stress. Autophagy relieves the stress by removing oxidative protein adducts, protein aggregates, and damaged mitochondria. We previously found that miR-29 is downregulated in choroid/RPE tissue in a model of exudative age-related macular degeneration (AMD), suggesting that miR-29 deficiency may contribute to autophagy inhibition and AMD progression. Here we wanted to test whether overexpression of miR-29 in RPEs could enhance autophagy, thereby facilitating removal of drusen components. Indeed, overexpression of miR-29 in the RPEs increased autophagy, assessed by decreased protein levels of p62, increased lipid form of microtubule-associated protein light chain (LC3-II), and elevated autophagy flux. Furthermore, overexpression of miR-29 mitigated the formation of mutant αB-crystallin (R120G) protein aggregates. In probing the mechanism, we demonstrated that miR-29 post-transcriptionally repressed LAMPTOR1/p18 via targeting its 3'-UTRs of messenger RNA. MiR-29 overexpression and knockdown of LAMPTOR1/p18 led to limited mTORC1 recruitment to lysosomes and inhibition of mTORC1 activity. Altogether, miR-29 enhances autophagy which aids in removal of protein aggregates. These findings reveal a novel role of miR-29, which has the potential of being a therapeutic strategy for rescuing RPE degeneration in ocular disorders.


Assuntos
Autofagia/genética , Células Epiteliais/citologia , Células Epiteliais/metabolismo , MicroRNAs/metabolismo , Proteínas Mutantes/metabolismo , Epitélio Pigmentado da Retina/citologia , Cadeia B de alfa-Cristalina/metabolismo , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina e Hélice-Alça-Hélix Básicos/metabolismo , Núcleo Celular/metabolismo , Inibidor de Quinase Dependente de Ciclina p18/metabolismo , Citosol/metabolismo , Células HEK293 , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisossomos/metabolismo , Alvo Mecanístico do Complexo 1 de Rapamicina/metabolismo , MicroRNAs/genética , Modelos Biológicos , Agregados Proteicos
18.
Int J Mol Med ; 42(5): 2437-2446, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-30226538

RESUMO

MicroRNAs (miRNAs) have a key role in the pathogenesis of pulmonary arterial hypertension (PAH), a disease characterized by enhanced proliferation and reduced apoptosis of pulmonary artery smooth muscle cells. In the present study, miR­760 was demonstrated to be downregulated in PAH lung tissues compared with normal lung tissues, an effect that may be associated with the development of PAH. Hypoxia is an important stimulus for human pulmonary artery smooth muscle cell (hPASMC) proliferation and the occurrence of PAH. Therefore, the effect of miR­760 in hypoxia­treated and normal hPASMCs was investigated. Expression of exogenous miR­760 decreased cell proliferation in hypoxia­induced hPASMCs, and promoted cell apoptosis with an increase in the BCL2 associated X/BCL2 ratio and the expression levels of Caspase­3 and Caspase­9. In addition, overexpression of miR­760 suppressed the migration of hPASMCs under hypoxic conditions. Furthermore, miR­760 was demonstrated to mediate its anti­proliferation effect via the regulation of toll­like receptor 4 (TLR4), a direct target of miR­760. The results revealed that knockdown of TLR4 restrained the hypoxia­induced hPASMC proliferation and induced cell apoptosis. The present study uncovered a novel regulatory pathway involving miR­760 and suggested that miR­760 may be explored as a potential therapy for PAH in the future.


Assuntos
Apoptose , Regulação da Expressão Gênica , MicroRNAs/genética , Miócitos de Músculo Liso/citologia , Artéria Pulmonar/citologia , Receptor 4 Toll-Like/genética , Hipóxia Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Regulação para Baixo , Humanos , Hipertensão Pulmonar/genética , Hipertensão Pulmonar/patologia , Miócitos de Músculo Liso/metabolismo , Miócitos de Músculo Liso/patologia , Artéria Pulmonar/metabolismo , Artéria Pulmonar/patologia
19.
Zhongguo Zhong Yao Za Zhi ; 43(12): 2556-2562, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29950075

RESUMO

Two new polypeptides were isolated and purified from the extract of deer bone (constitutive part of Cucumis and Cervus polypeptide injection) by various column chromatography including C4 300Å and Sephadex G-50, as well as semipreparative HPLC. Their N-terminal amino acid sequences were identified by De Novo sequencing on the basis of MALDI-TOF-MS data and Explorer™ software. The N-terminal amino acid sequences of polypeptides were identified as NH2-Gly-Pro-Val-Gly-Pro-Thr-Gly-Pro-Val-Gly-Ala-Ala-Gly-Pro-Ser-Gly-Pro-Asp (Mei18 peptide, 1) and NH2-Ala-Gly-Pro-Ala-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Leu-Gly-Pro-Pro-Asp-Ser-Try-Asp (Mei23 peptide, 2), respectively. Mei18 and Mei 23 peptides are new polypeptides.


Assuntos
Osso e Ossos/química , Cervos , Materia Medica/química , Peptídeos/química , Sequência de Aminoácidos , Animais , Espectrometria de Massas
20.
Chin Med J (Engl) ; 131(8): 927-932, 2018 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-29664052

RESUMO

Background: The co-existence of myasthenia gravis (MG) and thymoma makes the surgical treatment more complicated and adjuvant radiation more controversial. The aim of this study was to investigate adjuvant radiotherapy for thymoma with MG after extended thymectomy. Methods: A total of 181 patients with both MG and thymoma were recruited between 2003 and 2014 at Tongren Hospital, China. Among all the patients, 157 patients received radiation therapy after surgery (Group A); whereas the other 24 patients did not receive radiation therapy (Group B). According to the time that patients started mediastinal radiation therapy, we subdivided the 157 patients in Group A into subgroups (1-month subgroup, n = 98; 2-month subgroup, n = 7; and 3-month subgroup, n = 52). We then compared the effect of the mediastinal radiation therapy across these different groups using the survival rate, the rate of postoperative myasthenic crisis, and the complete stable remission (CSR) rate as the primary endpoints. Results: There was a significant difference in the occurrence of postoperative myasthenic crisis between 1-month subgroup and Group B (χ2 = 4.631, P = 0.031). The rates of reaching CSR were 32.6% in 1-month subgroup, 25% in 3-month subgroup, and 22.7% in Group B, respectively. The overall survival rates of 1-month subgroup, 3-month subgroup, and Group B were 88.8%, 83.3%, and 77.3%, respectively. Analysis on the Kaplan-Meier survival curves demonstrated that within 8 years after surgery, there was no significant difference in aspects of overall survival and disease-free survival between 1-month subgroup and Group B, and between 3-month subgroup and Group B; over 8 years after surgery, the disease-free survival rates in 1-month subgroup, 3-month subgroup and Group B were 79.4%, 70.6%, and 55.3%, respectively. Conclusions: Adjuvant radiation within 1 month after extended thymectomy may be helpful in controlling postoperative MG, such as decreasing the possibility of postoperative myasthenic crisis, and raising cumulative probabilities of reaching CSR.


Assuntos
Miastenia Gravis/cirurgia , Miastenia Gravis/terapia , Radioterapia Adjuvante/métodos , Timectomia/métodos , Timoma/cirurgia , Timoma/terapia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Neoplasias do Timo/cirurgia , Neoplasias do Timo/terapia , Resultado do Tratamento
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