Chlorogenic acid improves the development of porcine parthenogenetic embryos by regulating oxidative stress and ameliorating mitochondrial function.

Chlorogenic acid (CGA) is an effective phenolic antioxidant that can scavenge hydroxyl radicals and superoxide anions. Herein, the protective effects and mechanisms leading to CGA-induced porcine parthenogenetic activation (PA) in early-stage embryos were investigated. Our results showed that 50 µM CGA treatment during the in vitro culture (IVC) period significantly increased the cleavage and blastocyst formation rates and improved the blastocyst quality of porcine early-stage embryos derived from PAs. Then, genes related to zygotic genome activation (ZGA) were identified and investigated, revealing that CGA can promote ZGA in porcine PA early-stage embryos. Further analysis revealed that CGA treatment during the IVC period decreased the abundance of reactive oxygen species (ROS), increased the abundance of glutathione and enhanced the activity of catalase and superoxide dismutase in porcine PA early-stage embryos. Mitochondrial function analysis revealed that CGA increased mitochondrial membrane potential and ATP levels and upregulated the mitochondrial homeostasis-related gene NRF-1 in porcine PA early-stage embryos. In summary, our results suggest that CGA treatment during the IVC period helps porcine PA early-stage embryos by regulating oxidative stress and improving mitochondrial function.

Biflavonoids from Ginkgo biloba leaves as a novel anti-atherosclerotic candidate: Inhibition potency and mechanistic analysis.

BACKGROUND: Ginkgo biloba L. is one of the oldest trees on earth, and its leaves have been used since ages as herbal medicine to treat cerebrovascular disorders. It is worth noting that in addition to the widely concerned flavonoids and terpenoids, it also contains various thus far neglected biflavonoids. In fact, biflavonoids are flavonoids consisting of apigenin or its derivatives as monomeric scaffold, and are linked via C-C or C-O-C bond. PURPOSE: Based on the structural similarity of flavonoids, we hypothesized that biflavonoids may play a potential role in the treatment of cerebrovascular diseases. Here, we describe the effectiveness and underlying mechanisms for prevention and treatment of atherosclerosis (AS) by biflavonoids. STUDY DESIGN AND METHODS: Four main biflavonoids in Ginkgo biloba leaves were screened by oleic acid-induced lipid production in HepG2 cells. The non-covalent effects of biflavonoids on the potential targets of atherosclerosis were screened by reverse targeting and molecular dynamics simulation. The interactions between biflavonoids and potential targets were evaluated by an exogenous cell model, which verified the consistency of the simulation results. CONCLUSION: Among all four biflavonoids, ginkgetin significantly inhibited oleic acid-induced lipid production in HepG2 cells and reduced total cholesterol and triglyceride levels. The interaction of ginkgetin with CDK2 through π-alkyl and hydrogen bonds increased the binding of molecules and proteins. Ginkgetin arrested the cells in the G1-S phase, which significantly inhibited abnormal cell growth which closely related to the occurrence and development of atherosclerosis. Biflavonoids could be a promising natural medicine for the treatment of atherosclerosis.

Late-Onset Bartter Syndrome Type II Due to a Novel Compound Heterozygous Mutation in KCNJ1 Gene: A Case Report and Literature Review.

Background: Bartter syndrome (BS) type II is a rare autosomal recessive renal tubular disorder caused by mutations in the KCNJ1 gene, which encodes the apical renal outer medullary potassium (ROMK) channel in the thick ascending limb (TAL) of Henle's loop. BS type II is typically considered as a disorder of infancy and seldom seen in adults. Case Presentation: A 34-year-old woman was admitted with generalized body numbness and hand convulsions, without growth retardation. Laboratory tests revealed hypokalemic metabolic alkalosis, hyperreninemic hyperaldosteronism, and nephrocalcinosis. She was misdiagnosed during the initial diagnosis process and was finally diagnosed with late-onset BS type II via genetic testing through next-generation sequencing combined with Sanger sequencing. A novel compound heterozygous p.Leu207Ile/p. Cys308Arg variant in exon 5 of the KCNJ1 gene from her parents was identified and speculated to be a potential pathogenic gene variation. Conclusion: We report a case of late-onset BS type II with a novel compound heterozygous mutation in KCNJ1. Both variants are novel and have never been reported. Our report will have a significant impact on the diagnosis of BS in other patients without typical clinical presentations and emphasizes the importance of genetic investigation.

Action Mechanism Underlying Improvement Effect of Fuzi Lizhong Decoction on Nonalcoholic Fatty Liver Disease: A Study Based on Network Pharmacology and Molecular Docking.

OBJECTIVE: This study aimed to decipher the bioactive compounds and potential mechanism of traditional Chinese medicine (TCM) formula Fuzi Lizhong Decoction (FLD) for nonalcoholic fatty liver disease (NAFLD) treatment via an integrative network pharmacology approach. METHODS: The candidate compounds of FLD and its relative targets were obtained from the TCMSP and PharmMapper web server, and the intersection genes for NAFLD were discerned using OMIM, GeneCards, and DisGeNET. Then, the PPI and component-target-pathway networks were constructed. Moreover, GO enrichment and KEGG pathway analysis were performed to investigate the potential signaling pathways associated with FLD's effect on NAFLD. Eventually, molecular docking simulation was carried out to validate the binding affinity between potential core components and key targets. RESULTS: A total of 143 candidate active compounds and 129 relative drug targets were obtained, in which 61 targets were overlapped with NAFLD. The PPI network analysis identified ALB, MAPK1, CASP3, MARK8, and AR as key targets, mainly focusing on cellular response to organic cyclic compound, steroid metabolic process, and response to steroid hormone in the biological processes. The KEGG pathway analysis demonstrated that 16 signaling pathways were closely correlated with FLD's effect on NALFD with cancer pathways, Th17 cell differentiation, and IL-17 signaling pathways as the most significant ones. In addition, the molecular docking analysis revealed that the core active compounds of FLD, such as 3'-methoxyglabridin, chrysanthemaxanthin, and Gancaonin H, had a high binding activity with such key targets as ALB, MAPK1, and CASP3. CONCLUSIONS: This study suggested that FLD exerted its effect on NAFLD via modulating multitargets with multicompounds through multipathways. It also demonstrated that the network pharmacology-based approach might provide insights for understanding the interrelationship between complex diseases and interventions of the TCM formula.

Botanical characteristics, phytochemistry and related biological activities of Rosa roxburghii Tratt fruit, and its potential use in functional foods: a review.

Due to the growing global population, reduction in arable land and effects of climate change, incongruity between food supply and demand has become increasingly severe. Nowadays, with awareness of the elementary nutrients required for human growth, increasing attention is being paid to the health and medical functions of food. Along with increased food production achieved by modern agricultural techniques, underutilised functional foods are an important strategy for solving food security problems and maintaining the nutritional quality of the human diet. Rosa roxburghii Tratt (RRT) is a natural fruit that contains unique functional and nutritional constituents, which are characterised by a high anti-oxidant potential. This review summarises the biological characteristics, chemical composition, health-promoting properties and development status of RRT products to inspire investigations on the use of RRT fruit as a functional food, dietary supplement and pharmaceutical additive. The nutrients and functional ingredients of RRT fruit are described in detail to provide more reference information for nutritionists and pharmacists.

A novel idea for establishing Parkinson's disease mouse model by intranasal administration of paraquat.

Background: In this study, we sought to provide an idea for establishing a novel mouse model for Parkinson's disease (PD) through intranasal administration of paraquat instead of the conventional method of intraperitoneal injection. Intranasal administration has the potential to lower mortality caused by intraperitoneal paraquat administration.Methods: A paraquat-loaded thermosensitive hydrogel composed of poloxamer 407 and poloxamer 188 was prepared. The survival rate of the animals was monitored upon paraquat administration nasally and intraperitoneally. The animals' behavior was also observed. Immunofluorescence staining of tyrosine hydroxylase (TH) - positive cells and western blotting of α-synuclein (α-syn)in striatum were performed. HPLC method with electrochemical detection was used to quantify monoamine neurotransmitters in striatum. Real-time RT-PCR analysis of type 1 collagen, type 3 collagen and fibronectin expression was used to evaluate pulmonary fibrosis in mice after paraquat administration.Results: The results indicated that intranasal administration of paraquat-loaded thermosensitive hydrogel can elicit Parkinsonism-like symptoms in mice. Relative to the conventional intraperitoneal injection, this strategy significantly improves survival when modeling PD and resulted in a higher loss of TH positive neurons in substantia nigra pars compacta (SNpc) and more aggregation of α-syn in striatum. Moreover, animals receiving paraquat hydrogel nasally exhibited motor disorder as well as lower levels of dopamine and dopamine metabolites in striatum when compared to those receiving paraquat intraperitoneally. The mRNA expression of collagen and fibronectinindicated that intranasal administration of paraquat was not associated with lung fibrosis.Conclusion: This strategy provides a new idea and more convenient operation for the future study of mouse model of PD.

Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: A systematic review.

OBJECTIVE: Psychogenic non-epileptic seizures (PNES) are conversion disorders with functional neurological symptoms that can resemble epileptic seizures (ES). We conducted a systematic review to obtain an overview of the value of prolactin (PRL) levels in the differential diagnosis between PNES and ES. METHODS: We searched PubMed, EMBASE, and Cochrane Library databases for studies published up to June 4th, 2020. Published studies were included if they fulfilled the following criteria: original research on PRL changes after ES and PNES. By applying Bayes' theorem, we calculated the predicted values of PRL with pretest probabilities of 90 % and 75 % in ES. RESULTS: Sixteen studies were included in this review. All the studies showed that PRL levels increase after ES, especially 10-20 min after ES, when the elevation was most obvious. In studies where capillary PRL level measurements were included, the median sensitivity in the diagnosis of ES (all epileptic seizure types), generalized tonic clonic seizures (GTCS), focal impaired awareness seizures (FIAS), and focal aware seizures (FAS) was 67.3 %, 66.7 %, 33.9 %, and 11.1 %, respectively. The median specificity in the diagnosis of ES was 99.1 %. By using Bayes' theorem, when we used the median specificity and sensitivity for predictive value calculation, assuming a pretest probability of 90 %, a positive PRL measure was highly predictive (99 %) of all types of ES, and negative predictive values were all below 30 %. When we used the lowest specificity and sensitivity for predictive value calculation, assuming a pretest probability of 75 %, ES and GTCS had positive predictive values of 77.2 % and 81.0 %, respectively; the negative predictive values of PRL in ES and GTCS were 26.2 % and 29.6 %, respectively. CONCLUSIONS: The use of PRL could be a useful adjunct to differentiate GTCS from PNES. However, PRL levels are of limited use for differentiating FIAS or FAS from PNES, and a negative PRL measure is not predictive of PNES.

Use of the modified Glasgow Coma Scale score to guide sequential invasive-noninvasive mechanical ventilation weaning in patients with AECOPD and respiratory failure.

Sequential invasive-noninvasive ventilation (NIV) improves the outcomes of patients with respiratory failure caused by acute exacerbation of chronic obstructive pulmonary disease (AECOPD); however, there is no clear consensus on the optimal timing of the switch to sequential invasive-NIV in these patients. In the present study, a potential role for the modified Glasgow Coma Scale (GCS) score to guide sequential weaning was investigated. Patients with AECOPD and respiratory failure were prospectively recruited from three study centers (Wenling Hospital Affiliated to Wenzhou Medical University, the First Affiliated Hospital of Wenzhou Medical University and Changsha Central Hospital) between January 1st 2016 and December 31st 2018. Patients were randomly assigned to group A and B, with the switching point for sequential weaning strategy in the two groups being a modified GCS score ≥13 and 10 points, respectively. Each group included 240 patients. Baseline demographic characteristics were comparable in the two groups. The duration of invasive mechanical ventilation (IMV) in group A was significantly shorter than that in group B. However, there were no significant between-group differences with respect to the incidence of re-intubation, ventilator-associated pneumonia, in-hospital mortality or the length of hospital stay. Use of a modified GCS score ≥13 as the switching point for sequential invasive-NIV may help decrease the duration of IMV in patients with AECOPD and respiratory failure.

Efficacy of the ketogenic diet in patients with Dravet syndrome: A meta-analysis.

PURPOSE: Dravet syndrome is an infantile epilepsy syndrome with drug resistant seizures and cognitive impairment. The aim of this meta-analysis was to summarize the findings of relevant published studies to identify the efficacy of a ketogenic diet in patients with Dravet syndrome and their compliance thereof, and to provide useful information for clinical practice. METHODS: The PubMed, Embase, Wanfang, and CNKI databases were searched for relevant studies published up to September 25, 2019; the included studies were reviewed. Meta-analyses were performed using R software to determine the combined efficacy rates and retention rate for the ketogenic diet in patients with Dravet syndrome. RESULTS: Seven studies involving 167 patients met the inclusion criteria: four were retrospective studies, and three were prospective studies. The meta-analysis revealed that 63 %, 60 %, and 47 % of responder patients achieved ≥50 % seizure reduction at month 3, 6, and 12, respectively. The pooled retention rate of the ketogenic diet at month 6 and month 12 was 78 % and 49 %, respectively. CONCLUSIONS: Our meta-analysis indicates that the ketogenic diet is a treatment option for patients with Dravet syndrome. The ketogenic diet is safe and its adverse effects are mostly acceptable. However, further investigations, especially high-quality controlled trials with large samples, are required.

Bibliometrics and Visualization of the Mechanisms of Parkinson's Diseases Based on Animal Models.

OBJECTIVE: Energy metabolism disorder is one of the causes of Parkinson's disease (PD). Rodents, such as rats and mice are often used to establish animal models of PD. This paper used a bibliometric method to analyze the studies of rat and mouse PD models published between 2009 and 2018 in the Web of Science (WOS) database using CiteSpace V software. In addition, we conducted a literature review on the development status and research hotspots in this field in the past ten years. METHODS: The related articles on rat and mouse PD models were retrieved from the WOS database, and an analysis of the keywords in these articles was conducted using CiteSpace V. A timeline graph was developed by the software in order to show the focus of researchers in the PD field. RESULTS: A total of 8,636 articles were obtained. Results of the cluster analysis in the PD field such as neuroinflammation, oxidative stress, and autophagy, contributed to the systematic review about the pathogenesis of PD. At the same time, based on the property of the model drug, this review has summarized and compared different administration techniques and mechanisms of 6-hydroxydopamine (6- OHDA), 1-methyl-4-phenyl-1, 2, 4, 5-tetrahydropyridine (MPTP), paraquat and rotenone. CONCLUSION: According to the bibliometric analysis, studies on PD were focused on the mechanisms of oxidative stress, neuroinflammation, and autophagy. Activated microglia releases inflammatory cytokines; mitochondrial dysfunction is caused by oxidative damage of mitochondrial protein; abnormal autophagy-lysosome pathway can lead to abnormal protein deposition in dopaminergic neurons. In addition, although many animal models of PD have been established, there are some limitations of such models. Therefore, it is necessary to develop models that accurately mimic human PD.

Anti-Inflammatory Effects of Neochlorogenic Acid Extract from Mulberry Leaf (Morus alba L.) Against LPS-Stimulated Inflammatory Response through Mediating the AMPK/Nrf2 Signaling Pathway in A549 Cells.

Neochlorogenic acid (nCGA) is a phenolic compound isolated from mulberry leaf (Morus alba L.), which possesses multiple pharmacological activities containing antioxidant and anti-inflammatory effects. However, the role of nCGA in the treatment of acute pneumonia and the underlying molecular mechanism are still unclear. Hence, the aim of study is to investigate the anti-inflammatory properties of nCGA on LPS-stimulated inflammation in A549 cells. In the present study, results reported that nCGA without cytotoxicity significantly reduced the production of TNF-α, IL-6, and NO, and further suppressed the proteins of iNOS, COX2, TNF-α, IL-6 expression. Furthermore, nCGA also inhibited NF-κB activation and blocked MAPKs signaling pathway phosphorylation. In addition, we found nCGA significantly increased the expression of HO-1 via activating the AMPK/Nrf2 signaling pathway to attenuate the inflammatory response, whereas this protective effect of nCGA was reversed by pre-treatment with compound C (C.C, an AMPK inhibitor). Therefore, all these results indicated that nCGA might act as a natural anti-inflammatory agent for the treatment of acute pneumonia.

Antioxidant Activities of Quercetin and Its Complexes for Medicinal Application.

Quercetin is a bioactive compound that is widely used in botanical medicine and traditional Chinese medicine due to its potent antioxidant activity. In recent years, antioxidant activities of quercetin have been studied extensively, including its effects on glutathione (GSH), enzymatic activity, signal transduction pathways, and reactive oxygen species (ROS) caused by environmental and toxicological factors. Chemical studies on quercetin have mainly focused on the antioxidant activity of its metal ion complexes and complex ions. In this review, we highlight the recent advances in the antioxidant activities, chemical research, and medicinal application of quercetin.

One bis-indole alkaloid-voacamine from Voacanga africana Stapf: biological activity evaluation of PTP1B in vitro utilizing enzymology method based on SPRi expriment.

One known bis-indole alkaloid-voacamine was isolated from Voacanga africana Stapf and Surface Plasmon Resonance imaging (SPRi) exprement showed that this alkaloid could be combine with Protein Tyrosine Phosphatase1B (PTP1B). Then the PTP1B activity inhibition experiment display that the compound showed an outstanding promoting activity to PTP1B.

Primary small cell neuroendocrine carcinoma of the Bartholin's gland: A case report.

Primary carcinoma of the Bartholin's gland (BG) is a rare malignancy. There are extremely rare cases of small cell neuroendocrine carcinoma (SCNC) of the BG reported in the English literature. A postmenopausal female presented with a 1-month history of increasing pain and swelling on the left vulva consistent with spontaneously bleeding. Pathology identified SCNC that arose in BG. The patient was treated with a radical wide local excision and bilateral inguinal lymph node dissection followed by six courses of chemotherapy. One month after primary treatment, without any pelvic recurrence or abnormal tumor markers indications, distant metastasis of the liver was diagnosed and VI hepatic lobectomy was performed. The patient maintained regular adjuvant chemotherapy every month under outpatient surveillance and has no local recurrence or distant metastasis.

Differences between motor execution and motor imagery of grasping movements in the motor cortical excitatory circuit.

BACKGROUND: Both motor imagery (MI) and motor execution (ME) can facilitate motor cortical excitability. Although cortical excitability is modulated by intracortical inhibitory and excitatory circuits in the human primary motor cortex, it is not clear which intracortical circuits determine the differences in corticospinal excitability between ME and MI. METHODS: We recruited 10 young healthy subjects aged 18-28 years (mean age: 22.1 ± 3.14 years; five women and five men) for this study. The experiment consisted of two sets of tasks involving grasp actions of the right hand: imagining and executing them. Corticospinal excitability and short-interval intracortical inhibition (SICI) were measured before the interventional protocol using transcranial magnetic stimulation (baseline), as well as at 0, 20, and 40 min (T0, T20, and T40) thereafter. RESULTS: Facilitation of corticospinal excitability was significantly greater after ME than after MI in the right abductor pollicis brevis (APB) at T0 and T20 (p < 0.01 for T0, and p < 0.05 for T20), but not in the first dorsal interosseous (FDI) muscle. On the other hand, no significant differences in SICI between ME and MI were found in the APB and FDI muscles. The facilitation of corticospinal excitability at T20 after MI correlated with the Movement Imagery Questionnaire (MIQ) scores for kinesthetic items (Rho = -0.646, p = 0.044) but did not correlate with the MIQ scores for visual items (Rho = -0.265, p = 0.458). DISCUSSION: The present results revealed significant differences between ME and MI on intracortical excitatory circuits of the human motor cortex, suggesting that cortical excitability differences between ME and MI may be attributed to the activation differences of the excitatory circuits in the primary motor cortex.

Internet addiction detection rate among college students in the People's Republic of China: a meta-analysis.

BACKGROUND: With the development of economy and technology, the Internet is becoming more and more popular. Internet addiction has gradually become a serious issue in public health worldwide. The number of Internet users in China has reached 731 million, with an estimated 24 million adolescents determined as having Internet addiction. In this meta-analysis, we attempted to estimate the prevalence of Internet addiction among College Students in the People's Republic of China in order to improve the mental health level of college students and provide evidence for the prevention of Internet addiction. METHODS: Eligible articles about the prevalence of Internet addiction among college students in China published between 2006 and 2017 were retrieved from online Chinese periodicals, the full-text databases of Wan Fang, VIP, and the Chinese National Knowledge Infrastructure, as well as PubMed. Stata 11.0 was used to perform the analyses. RESULTS: A total of 26 papers were included in the analyses. The overall sample size was 38,245, with 4573 diagnosed with Internet addiction. The pooled detection rate of Internet addiction was 11% (95% confidence interval [CI] 9-13%) among college students in China. The detection rate was higher in male students (16%) than female students (8%). The Internet addiction detection rate was 11% (95% CI 8-14%) in southern areas, 11% (95% CI 7-14%) in northern areas, 13% (95% CI 8-18%) in eastern areas and 9% (95% CI 8-11%) in the mid-western areas. According to different scales, the Internet addiction detection rate was 11% (95% CI 8-15%) using the Young scale and 9% (95% CI 6-11%) using the Chen scale respectively. Cumulative meta analysis showed that the detection rate had a slight upward trend and gradually stabilized in the last 3 years. CONCLUSION: The pooled Internet addiction detection rate of Chinese college students in out study was 11%, which is higher than in some other countries and strongly demonstrates a worrisome situation. Effective measures should be taken to prevent further Internet addiction and improve the current situation.

Nutrient-induced antibiotic resistance in Enterococcus faecalis in the eutrophic environment.

Nutrient deposition and extensive use of antibiotics are increasing worldwide, especially in freshwater ecosystems. Bacteria display resistance to certain antibiotics and thus survive for extended periods in eutrophic environments. In this study, model ecosystems were established to investigate the effect of nitrate and phosphate nutrient salts on antibiotic resistance in strains of Enterococcus faecalis. Mesocosms were replicated to evaluate the ecological effects of nutrient influx. The mesocosms were divided into four different nitrogen (N) and phosphorus (P) regimens. Enterococcus faecalis strains were isolated on Days 0, 1, 7, 14, 21, 28, 40, 60 and 95 to evaluate their sensitivity to ampicillin, oxytetracycline (OXY), ciprofloxacin (CIP), chloramphenicol (CHL), vancomycin and erythromycin (ERY). Resistance genes for ERY (ermB, msrC and mefA), OXY [tet(M), tet(L) and tet(S)] and CHL (cat) as well as the enterococcal surface protein gene (esp) were investigated by PCR. The total nitrogen, total phosphorus, chemical oxygen demand permanganate index (CODMn), chlorophyll-a, Secchi depth and trophic level index were observed. In conclusion, addition of N and P had a significant influence on the resistance phenotypes of E. faecalis to OXY, CHL and ERY. Only high dosage led to CIP resistance. Higher total N concentrations resulted in the development of relatively higher resistance to OXY and CIP. The resistance genes tet(L) and tet(S) for OXY, msrC for ERY and cat for CHL were found to be associated with resistance in E. faecalis.