Amygdalin and exercise training exert a synergistic effect in improving cardiac performance and ameliorating cardiac inflammation and fibrosis in a rat model of myocardial infarction.

This study investigated the effects of amygdalin (AMY, a cyanogenic glycoside widely distributed in the fruits and seeds of Rosaceae plants) on cardiac performance and ventricular remodeling in a rat model of myocardial infarction (MI). We also investigated whether the combination of AMY with exercise training (ExT) has a beneficial synergistic effect in treating MI rats. MI was induced by the ligation of the left anterior descending coronary artery in male SD rats. ExT or AMY treatment was started 1 week after MI and continued for 1 week (short-term) or 8 weeks (long-term). Cardiac function was evaluated by echocardiographic and hemodynamic parameters. Heart tissues were harvested and subjected to 2,3,5-triphenyl-tetrazolium chloride, Masson's trichrome, hematoxylin-eosin, and immunohistochemical staining. Gene expression was determined by quantitative polymerase chain reaction. Western blot gave a qualitative assessment of protein levels. AMY or ExT improved cardiac function and reduced infarct size in MI rats. AMY or ExT also suppressed myocardial fibrosis and attenuated inflammation in the infarct border zone of hearts from MI rats, as evidenced by inhibition of collagen deposition, inflammatory cell infiltration, and pro-inflammatory markers (interleukin 1ß, interleukin 6, tumor necrosis factor-α, and cyclooxygenase 2). Notably, the effects of AMY combined with ExT were superior to those of AMY alone or ExT alone. Mechanistically, these beneficial functions were correlated with the inhibition of MI-induced activation of the transforming growth factor-ß/Smad pathway. Collectively, AMY and ExT exert a synergistic effect on improving cardiac performance and ameliorating cardiac inflammation and fibrosis after MI, and the effects of long-term intervention were better than short-term intervention.

Light scattering of a uniform uniaxial anisotropic sphere by an on-axis high-order Bessel vortex beam.

Analytical solutions to the scattering of a uniform uniaxial anisotropic sphere illuminated by an on-axis high-order Bessel vortex beam (HOBVB) are investigated. Using the vector wave theory, the expansion coefficients of the incident HOBVB in terms of the spherical vector wave functions (SVWFs) are obtained. According to the orthogonality of the associated Legendre function and exponential function, more concise expressions of the expansion coefficients are derived. It can reinterpret the incident HOBVB faster compared with the expansion coefficients of double integral forms. The internal fields of a uniform uniaxial anisotropic sphere are proposed in the integrating form of the SVWFs by introducing the Fourier transform. The differences of scattering characteristics of a uniaxial anisotropic sphere illuminated by a zero-order Bessel beam, Gaussian beam, and HOBVB are exhibited. Influences of the topological charge, conical angle, and particle size parameters on the angle distributions of the radar cross section are analyzed in detail. The scattering and extinction efficiencies varied with the particle radius, conical angle, permeability, and dielectric anisotropy are also discussed. The results provide insights into the scattering and light-matter interactions and may find important applications in optical propagation and optical micromanipulation of biological and anisotropic complex particles.

Differential expression and functional analysis of circRNA in the ovaries of Yili geese at different egg-laying stages.

BACKGROUND: Ovarian development is regulated by genes that are expressed dynamically and stage-specifically. Circular RNA (circRNA) has been proven to play a significant role in the regulation of animal reproduction. OBJECTIVE: Studying the expression characteristics of circRNAs in goose ovaries at various egg-laying stages can provide a reference for the molecular regulation mechanism of ovary development in geese that is mediated by circRNAs. METHODS: In this study, the expression profiles of circRNAs were compared in ovary tissues from Yili geese in three different breeding periods, namely the prelaying period (KL), laying period (CL), and ceased period (XL), and differentially expressed circRNAs related to ovarian development in Yili geese were screened. The potential biological functions of differential circRNAs were predicted by bioinformatics, and the differential circRNA-miRNA regulatory network was constructed. RESULTS: The results showed that a total of 4483 circRNAs were identified in 12 ovarian tissue samples from Yili geese at different laying stages. In the KL vs. CL, XL vs. CL, and XL vs. KL groups, 159, 455, and 383 differentially expressed circRNAs were identified, respectively. The host genes of the differential circRNAs were mostly enriched in the signal transduction, metabolism, and other related pathways, such as those for phototransduction, glycerophospholipid metabolism, aminoacyl-tRNA biosynthesis, and retinol metabolism. Finally, we constructed circRNA-miRNA regulation networks. Nine differential circRNAs were randomly selected for qRT-PCR verification, and the expression trends were consistent with the sequencing results. CONCLUSIONS: Our results indicated that significant differences in the expression profiles of circRNAs in the ovaries of Yili geese at different egg-laying stages. Meanwhile, through analyzing the differential circRNA-miRNA interaction network, core regulators such as circRNA NW_013186107.1:36835|52,574 and gga-miR-34b-5p were screened. This study provides a reference for the further analysis of the molecular regulatory mechanism of the circRNAs regulating goose ovary development and enriches the theory of genetic regulation during goose ovary development.

A prospective trial to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with arsenic trioxide and carboplatin in locally advanced cervical cancer: a study protocol for randomized controlled clinical.

BACKGROUND: Cervical cancer is the fourth most common malignancy in women, which is threatening female reproductive tract health. Chemotherapy can be used for neoadjuvant therapy of locally advanced cervical cancer and postoperative adjuvant therapy for patients with high-risk factors, so as to reduce the focus, sensitize radiotherapy, and reduce recurrence. The current first-line treatment is paclitaxel combined with platinum. Many literature studies have found that As2O3 alone or in combination with platinum drugs have good efficacy in a variety of tumors both in vivo and in vitro. Moreover, our research group has verified that the efficacy of As2O3 combined with platinum drugs in the treatment of cervical cancer is not inferior to the traditional first-line regimen at the cellular and animal levels, and paclitaxel is more expensive than As2O3. Hence, we aim to evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. METHODS: Sixty participants in the IB2, IIA2, and IIB stages of cervical cancer will be recruited in this study. After excluding patients who did not meet the criteria, they were randomly assigned to two groups in a 1:1 ratio. All patients underwent colposcopic biopsies to confirm the diagnosis and detailed clinical examinations. Eligible patients will receive either 2 cycles of paclitaxel and carboplatin or As2O3 and carboplatin every 3 weeks. Patients were assessed for clinical efficacy after the second cycle of chemotherapy. Patients who had disease stable or disease progression at these time points will receive concurrent chemotherapy and radiation directly, while responders will receive PiverRutledge grade III radical hysterectomy and bilateral pelvic lymphadenectomy. Both groups of patients undergoing radical hysterectomy were given adjuvant therapy as per protocol-defined criteria. The efficacy and toxicity of the two groups were evaluated according to WHO acute and subacute toxicity classification standards. DISCUSSION: This is the first single-center, prospective, two-arm design, open-label randomized control trial that will evaluate the clinical efficacy and safety of neoadjuvant chemotherapy with As2O3 and carboplatin in locally advanced cervical cancer. TRIAL REGISTRATION: ChineseClinicalTrialRegistry ChiCTR1900023822 . Registered on 13 June 2019.

Nexmifa Regulates Axon Morphogenesis in Motor Neurons in Zebrafish.

Nexmif is mainly expressed in the central nervous system (CNS) and plays important roles in cell migration, cell to cell and cell-matrix adhesion, and maintains normal synaptic formation and function. Nevertheless, it is unclear how nexmif is linked to motor neuron morphogenesis. Here, we provided in situ hybridization evidence that nexmifa (zebrafish paralog) was localized to the brain and spinal cord and acted as a vital regulator of motor neuron morphogenesis. Nexmifa deficiency in zebrafish larvae generated abnormal primary motor neuron (PMN) development, including truncated Cap axons and decreased branches in Cap axons. Importantly, RNA-sequencing showed that nexmifa-depleted zebrafish embryos caused considerable CNS related gene expression alterations. Differentially expressed genes (DEGs) were mainly involved in axon guidance and several synaptic pathways, including glutamatergic, GABAergic, dopaminergic, cholinergic, and serotonergic synapse pathways, according to Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. In particular, when compared with other pathways, DEGs were highest (84) in the axon guidance pathway, according to Organismal Systems. Efna5b, bmpr2b, and sema6ba were decreased markedly in nexmifa-depleted zebrafish embryos. Moreover, both overexpression of efna5b mRNA and sema6ba mRNA could partially rescued motor neurons morphogenesis. These observations supported nexmifa as regulating axon morphogenesis of motor neurons in zebrafish. Taken together, nexmifa elicited crucial roles during motor neuron development by regulating the morphology of neuronal axons.

Clinical effect of different maintenance doses of caffeine citrate in the treatment of preterm infants requiring assisted ventilation: a pilot multicenter study. / ä¸åŒç»´æŒå‰‚é‡æž¸æ©¼é ¸å’–å•¡å› å¯¹è¾ åŠ©é€šæ°”æ—©äº§å„¿çš„ç–—æ•ˆè¯„ä¼°ï¼šä¸€é¡¹åˆæ­¥å¤šä¸­å¿ƒç ”ç©¶.

OBJECTIVES: To explore the optimal maintenance dose of caffeine citrate for preterm infants requiring assisted ventilation and caffeine citrate treatment. METHODS: A retrospective analysis was performed on the medical data of 566 preterm infants (gestational age ≤34 weeks) who were treated and required assisted ventilation and caffeine citrate treatment in the neonatal intensive care unit of 30 tertiary hospitals in Jiangsu Province of China between January 1 and December 31, 2019. The 405 preterm infants receiving high-dose (10 mg/kg per day) caffeine citrate after a loading dose of 20 mg/kg within 24 hours after birth were enrolled as the high-dose group. The 161 preterm infants receiving low-dose (5 mg/kg per day) caffeine citrate were enrolled as the low-dose group. RESULTS: Compared with the low-dose group, the high-dose group had significant reductions in the need for high-concentration oxygen during assisted ventilation (P=0.044), the duration of oxygen inhalation after weaning from noninvasive ventilation (P<0.01), total oxygen inhalation time during hospitalization (P<0.01), the proportion of preterm infants requiring noninvasive ventilation again (P<0.01), the rate of use of pulmonary surfactant and budesonide (P<0.05), and the incidence rates of apnea and bronchopulmonary dysplasia (P<0.01), but the high-dose group had a significantly increased incidence rate of feeding intolerance (P=0.032). There were no significant differences between the two groups in the body weight change, the incidence rates of retinopathy of prematurity, intraventricular hemorrhage or necrotizing enterocolitis, the mortality rate, and the duration of caffeine use (P>0.05). CONCLUSIONS: This pilot multicenter study shows that the high maintenance dose (10 mg/kg per day) is generally beneficial to preterm infants in China and does not increase the incidence rate of common adverse reactions. For the risk of feeding intolerance, further research is needed to eliminate the interference of confounding factors as far as possible.

Sites and Regulation of L-Type Ca2+ Channel Cav1.2 Phosphorylation in Brain.

Cav1.2 channel phosphorylation plays an important role in regulating neuronal plasticity by action potential-dependent Ca2+ entry. Most studies of Cav1.2 regulation by phosphorylation have been reported in heart and muscles. Here, we identified phosphorylation sites of neuronal Cav1.2 channel protein purified from rat brain using mass spectrometry. The functional characterization of these phosphorylation sites showed altered voltage-dependent biophysical properties of the channel, without affecting current density. These results show that neuronal Cav1.2 channel is regulated by phosphorylation in a complex mechanism involving multiple phosphorylation sites.

Rapid Simultaneous Determination of 43 Pesticide Residues in Schizonepeta tenuifolia by Gas Chromatography Mass Spectrometry.

A simple, fast, and reliable method was established for simultaneous determination of 43 pesticides in Schizonepeta tenuifolia. The samples were prepared using solid-phase extraction (SPE) method. Pesticides were extracted from Schizonepeta tenuifolia using acetonitrile, cleaned with Pesticarb/NH2, and eluted by mixed solvents of acetonitrile and toluene (3 : 1, v/v). Selected pesticides were identified using DB-35MS capillary column and detected by gas chromatography mass spectrometry. Samples were quantified by external standard method. Recoveries for the majority of pesticides at spike levels of 0.2, 0.5, and 1 mg kg-1 ranged between 70 and 120% (except for Chlorothalonil, Thiamethoxam, and Dicofol), and the relative standard deviations (RSDs n = 6) were 1.32%-13.91%. Limits of detection (LODs) were 0.0011-0.0135 mg kg-1, whereas limits of quantification (LOQs) were 0.0038-0.0451 mg kg-1. The satisfactory accuracy and precision, in combination with a good separation and few interferences, have demonstrated the strong potential of this technique for its application in Schizonepeta tenuifolia analysis.

Protective effects of sevoflurane in cerebral ischemia reperfusion injury: a narrative review.

Ischemia/reperfusion (I/R) injury is a phenomenon that the reperfusion of ischemic organs or tissues aggravates their damage, which poses a serious health threat and economic burden to the world. I/R gives rise to a series of physiological and pathological world, including inflammatory response, oxidative stress, brain edema, blood-brain barrier destruction, and neuronal death. Therefore, finding effective treatment measures is extremely important to the recovery of I/R patients and the improvement of long-term quality of life. Sevoflurane is an important volatile anesthetic which has been reported to reduce myocardial I/R damage and infarct size. Sevoflurane also has anti-inflammatory and neuroprotective effects. As reported sevoflurane treatment could reduce nerve function injury, cerebral infarction volume and the level of inflammatory factors. At the same time, there is evidence that sevoflurane can reduce neuron apoptosis and antioxidant stress. The protective effect of sevoflurane in brain injury has been proved to be existed in several aspects, so that a comprehensive understanding of its neuroprotective effect is helpful to exploit new treatment paths for I/R, provide clinicians with new clinical treatment decisions, contribute to the effective treatment of I/R patients and the improvement of quality of life after I/R healing.

Cytotoxicity and Apoptosis Induced by Chenopodium ambrosioides L. Essential Oil in Human Normal Liver Cell Line L02 via the Endogenous Mitochondrial Pathway Rather Than the Endoplasmic Reticulum Stress.

Chenopodium ambrosioides L. (C. ambrosioides) has been used as dietary condiments and as traditional medicine in South America. The oil of Chenopodium ambrosioides L. (C. ambrosioides) can be used as a natural antioxidant in food processing. It also has analgesic, sedating, and deworming effects, and can be used along with the whole plant for its medical effects: decongestion, as an insecticide, and to offer menstruation pain relief. This study was conducted to investigate the cytotoxicity and apoptosis effects of an essential oil from C. ambrosioides in vitro. The cytotoxicity evaluation of the essential oil from C. ambrosioides on human normal liver cell line L02 was assessed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay. AO/EB dual fluorescent staining assay and Annexin V-FITC were used for apoptosis analysis. The changes in mitochondrial membrane potential (MMP) were analyzed with 5,5,6,6'-tetrachloro-1,1,3,3,-tetraethyl-imidacarbocyanine iodide (JC-1) dye under a fluorescence microscope. The level of apoptosis related protein expression was quantified by Western blot. The L02 cells were treated with the essential oil from C. ambrosioides at 24, 48, and 72 h, and the IC50 values were 65.45, 58.03, and 35.47 µg/mL, respectively. The AO/EB staining showed that viable apoptotic cells, non-viable apoptotic cells, and non-viable non-apoptotic cells appeared among the L02 cells under the fluorescence microscope. Cell cycle arrest at the S phase and cell apoptosis increased through flow cytometry in the L02 cells treated with the essential oil. MMP decreased in a concentration-dependent manner, as seen through JC-1 staining under the fluorescence microscope. In the L02 cells as shown by Western blot and qPCR, the amount of the apoptosis-related proteins and the mRNA expression levels of cytochrome C, Bax, Caspase-9, and Caspase-3 increased, Bcl-2 decreased, and Caspase-12, which is expressed in the endoplasmic reticulum, showed no obvious changes in protein amount or mRNA expression level. The essential oil form C. ambrosioides had a cytotoxic effect on L02 cells. It could inhibit L02 cell proliferation, arrest the cell cycle at the S phase, and induce L02 cell apoptosis through the endogenous mitochondrial pathway.

Analysis of radiation force on a uniaxial anisotropic sphere by dual counter-propagating Gaussian beams.

Based on Maxwell's stress tensor and the generalized Lorenz-Mie theory, a theoretical approach is introduced to study the radiation force exerted on a uniaxial anisotropic sphere illuminated by dual counter-propagating (CP) Gaussian beams. The beams propagate with arbitrary direction and are expanded in terms of the spherical vector wave functions (SVWFs) in a particle coordinate system using the coordinate rotation theorem of the SVWFs. The total expansion coefficients of the incident fields are derived by superposition of the vector fields. Using Maxwell stress tensor analysis, the analytical expressions of the radiation force on a homogeneous absorbing uniaxial anisotropic sphere are obtained. The accuracy of the theory is verified by comparing the radiation forces of the anisotropic sphere reduced to the special cases of an isotropic sphere. In order to study the equilibrium state, the effects of beam parameters, particle size parameters, and anisotropy parameters on the radiation force are discussed in detail. Compared with the isotropic particle, the equilibrium status is sensitive to the anisotropic parameters. Moreover, the properties of optical force on a uniaxial anisotropic sphere in a single Gaussian beam trap and Gaussian standing wave trap are compared. It indicates that the CP Gaussian beam trap may more easily capture or confine the anisotropic particle. However, the radiation force exerted on an anisotropic sphere exhibits very different properties when the beams do not propagate along the primary optical axis. The influence of the anisotropic parameter on the radiation force by CP Gaussian beams is different from that of a single Gaussian beam. In summary, even for anisotropic particles, the Gaussian standing wave trap also exhibits significant advantages when compared with the single Gaussian beam trap. The theoretical predictions of radiation forces exerted on a uniaxial anisotropic sphere by dual Gaussian beams provide effective ways to achieve the improvement of optical tweezers as well as the capture, suspension, and high-precision delivery of anisotropic particles.

Neuroprotective effect of helium after neonatal hypoxic ischemia: a narrative review.

Neonatal hypoxic ischemia is one of the leading causes of permanent morbidity and mortality in newborns, which is caused by difficulty in supplying blood and oxygen to brain tissue and is often associated with epilepsy, cerebral palsy, death, short-term or long-term neurological and cognitive impairment. In recent years, the clinical therapeutic effects of noble gases have been gradually discovered and recognized. Numerous studies have shown that noble gases have unique neuroprotective effects to restore damaged nerve and relieve symptoms in patients. Although research on the neuroprotective mechanisms of xenon and argon has yielded a lot of results, studies on helium have stalled. Helium is a colorless, odorless, monoatomic inert gas. The helium has no hemodynamic or neurocognitive side effects and can be used as an ideal pre-adaptor for future clinical applications. In recent years, studies have shown that heliox (a mixture of helium and oxygen) pretreatment can protect the heart, brain, liver and intestine from damage in several animal models, where a variety of signaling pathways have been proved to be involved. There are numerous studies on it even though the mechanism of helium for protecting newborns has not been fully elucidated. It is urgent to find an effective treatment due to the high death rate and disability rate of neonatal hypoxic ischemia. It is believed that helium will be approved safely and effectively for clinical use in the near future.

Axonal mRNA localization and local translation in neurodegenerative disease.

The regulation of mRNA localization and local translation play vital roles in the maintenance of cellular structure and function. Many human neurodegenerative diseases, such as fragile X syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, and spinal muscular atrophy, have been characterized by pathological changes in neuronal axons, including abnormal mRNA translation, the loss of protein expression, or abnormal axon transport. Moreover, the same protein and mRNA molecules have been associated with variable functions in different diseases due to differences in their interaction networks. In this review, we briefly examine fragile X syndrome, amyotrophic lateral sclerosis, Alzheimer's disease, and spinal muscular atrophy, with a focus on disease pathogenesis with regard to local mRNA translation and axon transport, suggesting possible treatment directions.

Correlation between corin, N-terminal pro-atrial natriuretic peptide and neonatal adverse prognostic in hypertensive disorders of pregnancy.

INTRODUCTION: Atrial natriuretic peptide (ANP) regulates water-salt balance and blood pressure by promoting renal sodium and water excretion. OBJECTIVE: Our study was to investigate plasma N-terminal pro-atrial natriuretic peptide (NT-proANP) and corin in hypertensive disorders of pregnancy (HDP) patients. Furthermore, the relationship between corin/NT-proANP and neonatal adverse prognosis were evaluated. METHODS: Seventy-seven HDP patients and forty-eight normotensive women as control group were recruited. Clinical characteristic and plasma were collected. Plasma NT-proANP and corin were determined by ELISA. Gestational age, neonatal weight and APGAR scores were recorded. Statistical analysis was conducted. RESULTS: NT-proANP and corin were significantly increased in HDP group compared with that of control (P < 0.05). NT-proANP and corin were significantly elevated in HDP patients who suffered from premature delivery (P < 0.05). Both NT-proANP and corin were negatively associated with delivery time, neonatal weight and APGAR scores in HDP group. Multiple regressions demonstrated that NT-proANP and corin were independent risk factor of delivery time, neonatal weight and APGAR scores. CONCLUSIONS: Plasma NT-proANP and corin were significantly increased in HDP. NT-proANP and corin were associated with neonatal adverse events in HDP patients. Thus, NT-proANP and corin may become new biomarkers for evaluating severity of pregnancy and neonatal adverse events in HDP patients.

Acyl-CoA synthetase long chain family member 4 plays detrimental role in early brain injury after subarachnoid hemorrhage in rats by inducing ferroptosis.

AIMS: Acyl-CoA synthetase long chain family member 4 (ACSL4) is closely related to tumor genesis and development in certain tissues. However, the function of ACSL4 in early brain injury (EBI) caused by subarachnoid hemorrhage (SAH) is unclear. In this study, we investigated the expression patterns and role of ACSL4 in SAH and post-SAH EBI using a rat model of SAH. METHODS: The rat model of SAH was induced by autologous blood injection into the prechiasmatic cistern of rats. We also used two specific inhibitors of ferroptosis (Ferrostatin-1 and Liproxstatin-1) to investigate the role of ferroptosis in EBI. RESULTS: We found that ACSL4 levels in brain tissue increased significantly in post-SAH EBI. Inhibiting the expression of ACSL4 using small interfering RNAs alleviated inflammation, blood-brain barrier (BBB) impairment, oxidative stress, brain edema, and behavioral and cognitive deficits, and increased the number of surviving neurons, after SAH. Similar effects were obtained by suppressing ferroptosis. CONCLUSIONS: ACSL4 exacerbated SAH-induced EBI by mediating ferroptosis. These findings may provide a theoretical basis for potential therapy aimed at alleviating post-SAH EBI.

In Silico Screening of Potential Spike Glycoprotein Inhibitors of SARS-CoV-2 with Drug Repurposing Strategy.

OBJECTIVE: To select potential molecules that can target viral spike proteins, which may potentially interrupt the interaction between the human angiotension-converting enzyme 2 (ACE2) receptor and viral spike protein by virtual screening. METHODS: The three-dimensional (3D)-coordinate file of the receptor-binding domain (RBD)-ACE2 complex for searching a suitable docking pocket was firstly downloaded and prepared. Secondly, approximately 15,000 molecular candidates were prepared, including US Food and Drug Administration (FDA)-approved drugs from DrugBank and natural compounds from Traditional Chinese Medicine Systems Pharmacology (TCMSP), for the docking process. Then, virtual screening was performed and the binding energy in Autodock Vina was calculated. Finally, the top 20 molecules with high binding energy and their Chinese medicine (CM) herb sources were listed in this paper. RESULTS: It was found that digitoxin, a cardiac glycoside in DrugBank and bisindigotin in TCMSP had the highest docking scores. Interestingly, two of the CM herbs containing the natural compounds that had relatively high binding scores, Forsythiae fructus and Isatidis radix, are components of Lianhua Qingwen (), a CM formula reportedly exerting activity against severe acute respiratory syndrome (SARS)-Cov-2. Moreover, raltegravir, an HIV integrase inhibitor, was found to have a relatively high binding score. CONCLUSIONS: A class of compounds, which are from FDA-approved drugs and CM natural compounds, that had high binding energy with RBD of the viral spike protein. Our work provides potential candidates for other researchers to identify inhibitors to prevent SARS-CoV-2 infection, and highlights the importance of CM and integrative application of CM and Western medicine on treating COVID-19.

Anesthetic efficacy of propofol combined butorphanol in laparoscopic surgery for ectopic pregnancy: A protocol of systematic review and meta-analysis.

BACKGROUND: Recent studies have suggested that propofol combined butorphanol (PB) has anesthetic effect in laparoscopic surgery (LS) for ectopic pregnancy (EP). But investigations of its potential effects are inconsistent. We will explore the current literature examining PB in LS for EP. METHODS: We will perform a comprehensive search from MEDLINE, Embase, Cochrane Library, PsycINFO, Global Health, Web of Science, Allied and Complementary Medicine Database, and China National Knowledge Infrastructure from inception to the present. Other literatures, such as conference abstracts, references to the relevant reviews will also be checked. Two authors will check the titles, abstracts, and full texts independently. They will also independently carry out data collection and study quality assessment. We will conduct statistical analysis using RevMan 5.3 software. RESULTS: This study will provide accurate results on the anesthetic effect and safety of PB in LS for EP. CONCLUSION: This study will establish high-quality evidence of the anesthetic effect and safety of PB in LS for EP to facilitate the clinical practice and guideline development. STUDY REGISTRATION NUMBER: INPLASY202040044.

MiR-29a in mesenchymal stem cells inhibits FSTL1 secretion and promotes cardiac myocyte apoptosis in hypoxia-reoxygenation injury.

BACKGROUND: Mesenchymal stem cells (MSCs) are under consideration for myocardial ischemia-reperfusion (I/R) injury therapy, but their mechanism remains to be evaluated. In this article, we aimed to study the effects of the miR-29a/follistatin-like 1 axis in bone marrow-derived mesenchymal stem cells on modulating myocyte apoptosis after hypoxia-reoxygenation (H/R) injury. METHODS: An in vitro myocardial ischemia-reperfusion injury model of H9c2 cells was developed by hypoxia-reoxygenation injury. The mRNA levels of follistatin-like 1, Bcl-2, Bax, and miR-29a and the protein levels of Bcl-2, Bax, cleaved caspase-3, and components of the JAK2/STAT3 pathway were detected by qRT-PCR and western blotting, respectively. Secretion of follistatin-like 1 was evaluated by enzyme-linked immunosorbent assay. Cell apoptosis was evaluated by flow cytometry. The interaction between miR-29a and follistatin-like 1 was evaluated by dual luciferase reporter assay. RESULTS: MiR-29a suppressed the expression and secretion of follistatin-like 1 in bone marrow-derived mesenchymal stem cells. Overexpression of follistatin-like 1 in bone marrow-derived mesenchymal stem cells decreased apoptosis of myocytes induced by hypoxia-reoxygenation. Cell apoptosis in myocytes was promoted by conditioned medium from bone marrow-derived mesenchymal stem cells with ectopic miR-29a expression. Conditioned medium of miR-29a-overexpressing bone marrow-derived mesenchymal stem cells inhibited the JAK2/STAT3 pathway in myocytes to promote apoptosis of myocytes. CONCLUSIONS: MiR-29a in bone marrow-derived mesenchymal stem cells inhibits follistatin-like 1 secretion and promotes myocyte apoptosis by suppressing the JAK2/STAT3 pathway in hypoxia-reoxygenation injury.

[7-hydroxy sulfonation of liquiritigenin by recombinant SULT1A3 enzyme and HEK-SULT1A3 cells].

In this study,liquiritigenin sulfonation was characterized using recombinant human sulfotransferases( SULTs). The chemical structure of liquiritigenin sulfate was determined by ultra-high performance liquid chromatography-quadrupole time-of-flight mass spectrometry( UPLC-Q-TOF-MS/MS). Then model fitting and parameter estimation were performed using the Graphpad Prism V5 software. Various SULT enzymes( SULT1 A1,1 A2,1 A3,1 B1,1 C2,1 C4,1 E1 and 2 A1) were able to catalyze the formation of liquiritigenin-7-O-sulfate. Sulfonation of liquiritigenin-7-hydroxy( 7-OH) by these eight SULT enzymes consistently displayed the classical Michaelis-Menten profile. According to the intrinsic clearance( CLint) value,the sulfonation rates of liquiritigenin-7-OH by expressed SULT enzymes followed the following rank order: SULT1 C4 > SULT1 A3 > SULT1 E1 > SULT1 A1 > SULT1 A2 > SULT1 B1 >SULT1 C2>SULT2 A1. Further,liquiritigenin-7-O-sulfonation was significantly correlated with the SULT1 A3 protein levels( P<0. 05).Then,human embryonic kidney( HEK) 293 cells over expressing SULT1 A3( named as HEK-SULT1 A3 cells) were conducted. As a result,liquiritigenin-7-O-sulfate( L-7-S) was rapidly generated upon incubation of the cells with liquiritigenin. Consistent with SULT1 A3,sulfonation of liquiritigenin-7-OH in HEK-SULT1 A3 cells also followed the Michaelis-Menten kinetics. The derived Vmaxvalues was( 0. 315±0. 009) µmol·min-1·g-1,Kmwas( 7. 04±0. 680) µmol·L-1,and CLintwas( 0. 045±0. 005) L·min-1·g-1. Moreover,the sulfonation characters of liquiritigenin( 7-OH) in SULT1 A3 were strongly correlated with that in HEK-SULT1 A3 cells( P<0. 001).The results indicated that HEK-SULT1 A3 cells have shown the catalytic function of SULT1 A3 enzymes. In conclusion,liquiritigenin was subjected to efficient sulfonation,and SULT1 A3 enzyme plays an important role in the sulfonation of liquiritigenin-7-OH. Significant sulfonation should be the main reason for the low bioavailability of liquiritigenin. In addition,HEK-SULT1 A3 cells were conducted and successfully used to evaluate liquiritigenin sulfonation,which will provide an appropriate tool to accurately depict the sulfonation disposition of liquiritigenin in vivo.

DKK1 inhibits breast cancer cell migration and invasion through suppression of ß-catenin/MMP7 signaling pathway.

BACKGROUND: DKK1 has been reported to act as a tumor suppressor in breast cancer. However, the mechanism of DKK1 inhibits breast cancer migration and invasion was still unclear. METHODS: Western blot and real time PCR was used to detect the expression of DKK1, ß-catenin and MMP7 in breast cancer cells. Wound scratch assay and transwell assay was employed to examine migration and invasion of breast cancer cell. RESULTS: DKK1 overexpression dramatically inhibits breast cancer cell migration and invasion. Knockdown of DKK1 promotes migration and invasion of breast cancer cells. DKK1 suppressed breast cancer cell migration and invasion through suppression of ß-catenin and MMP7 expression. XAV-939, an inhibitor of ß-catenin accumulation could reverse DKK1 silencing-induced MMP7 expression in breast cancer cells. Meanwhile, XAV-939 also could reverse the increase in the cell number invaded through Matrigel when DKK1 was knockdown. Furthermore, depletion of MMP7 also could reverse DKK1 knockdown-induced increase in the cell number invaded through Matrigel. CONCLUSIONS: DKK1 inhibits migration and invasion of breast cancer cell through suppression of ß-catenin/MMP7 pathway, our findings offered a potential alternative for breast cancer prevention and treatment.