Antioxidative, phytochemical and antimicrobial analysis of juices of eight citrus cultivars grown in Pakistan

Comparative nutritional analysis of citrus varieties cultivated in Pakistan has not been reported. Citrus is consumed all over the world due to its taste and also has pharmacological components. The present investigation evaluated the antioxidant, reducing power, total flavonoids and phenolics, DPPH free radical scavenging, protein kinase inhibition, and the antimicrobial activities of eight Pakistani citrus varieties. Grapefruit showed maximum total antioxidant potential (77 µg AAE/100 mg), followed by Kinnow and Shakri. Khatai showed maximum reducing power potential (69.6 µg AAE/100 mg) while Shakri and Grapefruit trailed it. All the varieties showed significant DPPH free radical scavenging activity. Maximum total phenolics in citrus juice were found in Shakri and Kinnow; 26.2 and 25.9 µg GAE/100mg, respectively. Variation in total flavonoids content was observed as Kinnow>Grapefruit>Shakri>Khatai. All the citrus juices showed mild to moderate antibacterial activity, while Mosambi and Malta contained potent antifungal components. HPLC analysis of citrus juices revealed that catechin was present in all citrus genotypes except Kinnow. The study concludes that citrus juices contain strong antioxidative potential, bear protein kinase inhibitors and can be used as cancer chemoprevention and supportive nutrition.

XYLANASE ACTIVITY OF ASPERGILLUS NIGER AT DIFFERENT ECOLOGICAL CONDITIONS

Maximization of xylanase activity at different media, temperature, pH and salt concentration has been presented in this paper. YpSs, Czapek dox and Malt extract medium were taken for evaluation of optimum growth and activity. Amongst all tested media, YpSs showed the highest growth. Three different natural carbon substitute i.e., wheat husk, rice husk and sugarcane baggase were used for xylanase activity. Maximum enzyme activity was observed in test fungus at rice husk. Production and maximum xylanase activity at rice husk has been observed at different temperatures, pH and Salt concentrations. The highest xylanase activity has been observed on day 5 at temperature 32° C, pH 6.5 and salt concentration of 2%.

Forecasting Ionospheric foF2 Based on Deep Learning Method

In this paper, a deep learning long-short-term memory (LSTM) method is applied to the forecasting of the critical frequency of the ionosphere F2 layer (foF2). Hourly values of foF2 from 10 ionospheric stations in China and Australia (based on availability) from 2006 to 2019 are used for training and verifying. While 2015 and 2019 are exclusive for verifying the forecasting accuracy. The inputs of the LSTM model are sequential data for the previous values, which include local time (LT), day number, solar zenith angle, the sunspot number (SSN), the daily F10.7 solar flux, geomagnetic the Ap and Kp indices, geographic coordinates, neutral winds, and the observed value of foF2 at the previous moment. To evaluate the forecasting ability of the deep learning LSTM model, two different neural network forecasting models: a back-propagation neural network (BPNN) and a genetic algorithm optimized backpropagation neural network (GABP) were established for comparative analysis. The foF2 parameters were forecasted under geomagnetic quiet and geomagnetic disturbed conditions during solar activity maximum (2015) and minimum (2019), respectively. The forecasting results of these models are compared with those of the international reference ionosphere model (IRI2016) and the measurements. The diurnal and seasonal variations of foF2 for the 4 models were compared and analyzed from 8 selected verification stations. The forecasting results reveal that the deep learning LSTM model presents the optimal performance of all models in forecasting the time series of foF2, while the IRI2016 model has the poorest forecasting performance, and the BPNN model and GABP model are between two of them.

Trabectedin (T) in desmoplastic small round cell tumor (DSRCT): Report of its effect in 3 relapsed patients (pts) and the comparison of different regimens in a patient-derived xenograft (PDX) model.

e23553 Background: DSRCT is an ultra-rare soft tissue sarcoma marked by the presence of the EWS-WT1 translocation and a dismal prognosis. Anecdotal activity of T in DSRCT pts was reported. We describe herein three advanced DSRCT pts treated with T and a comparative assessment of doxorubicin (D), pazopanib (P) and T in a patient-derived xenograft (PDX) model of DSRCT. Methods: Three pts (#1, #2 and #3) suffering from progressive, metastatic, unresectable relapsing disease from a primary peritoneal DSRCT previously treated with 8 cycles of anthracycline-based neoadjuvant chemo and complete surgical resection, were started on T (1.3 mcg/sqm every 3-4 weeks). A PDX model was generated by subcutaneously implanting small tumor fragments obtained at surgery from a treatment-naïve DSRCT patient into the right flank of SCID mice. Consistency of PDX and the originating tumor was confirmed in terms of histomorphology and presence of the EWS-WT1 gene fusion. Mice were randomized to receive D, P and T, administered as single agents at optimal doses and schedules. Drug activity was assessed in terms of tumor volume inhibition (TVI) percentage in treated versus control mice. An orthotopic xenograft model was also generated by injecting DSRCT cells into the peritoneal cavity of SCID mice. Results: At the time of this report, pt #1 and #2 are on therapy with T, with a partial response by RECIST maintained after 48 and 36 months from treatment start, respectively, while #3 progressed after 4 months. In the DSRCT PDX model, T was the most effective drug, with a maximum TVI of 82%, while D and P showed lower, comparable activity (maximum TVI: 59% and 66%, respectively). In the orthotopic DSRCT PDX, DSRCT cells spreading in the abdominal cavity generated different tumor masses, properly recapitulating the dissemination pattern in patients, confirming the reliability of this preclinical model. Conclusions: Both our preliminary model and our further clinical observations support the potential of T in DSRCT. A confirmatory prospective clinical study is now warranted.

Evaluation of the anti-diabetic activities of crude extracts of Annona muricata and Rutidea parviflora in alloxan-diabetic rats

Background: Diabetes Mellitus (DM), is a malignant disease that has impacted the globe in astronomical proportions. Chronic hyperglycemia is a major condition suffered by patients with DM. Currently, the cost of managing DM is highly exorbitant and poses a significant obstacle to many living with the disease in developing countries. Thus, the need for affordable alternatives with optimum potency and minimal side effects is justified. Historically, Annona muricata is one plant that is used in the treatment of DM and a host of other ailments. Rutidea parviflora has been used in combination with other plants in the treatment of DM by some ethnic groups. The aim of this study is to investigate the anti-diabetic activities of these plants. Method: The anti-diabetic activities of aqueous and organic extracts of Annona muricata (leaves), and Rutidea parviflora (root bark) at 200 mg/kg and 400 mg/kg, were screened for their anti-diabetic activities in normoglycemic and alloxan-induced diabetic rats (150-200 g) at 1h, 2h, 4h, 6h, 8h, and the 12th hour. DMSO (0.3 ml of 33.3% v/v stock) and Glibenclamide 10 mg/kg were administered to the control and reference groups respectively. Result: Organic extracts of A. muricata at 400 mg/kg significantly decreased FBGL in both normoglycemic and hyperglycemic groups by 65.9% and 62.1% respectively (P<0.05). R. parviflora leaves extracts showed less activity. However, it had relatively short acting activity (maximum activity at the 4th hour). In each case, the organic extracts performed better than the aqueous extracts. Conclusion: A. muricata has potentials for the treatment of DM, and merits further research to support the plant’s therapeutic application. R. parviflora may offer some beneficial effect, and possibly boost the potency of A. muricata by synergistic activity when co-administered.

A novel index for staging hepatitis B related liver cirrhosis in patients with hepatocellular carcinoma

Information on the stage of liver cirrhosis is essential for prognostication and decisions on surgical planning for hepatocellular carcinoma (HCC) patients. But a non-invasive liver cirrhosis staging model is still lacking. The aim of our study was to develop a non-invasive model based on routine clinical parameters to evaluate the severity of cirrhosis in hepatitis B related HCC patients. A total of 226 HCC patients with chronic hepatitis B virus (HBV) infection who had liver resection were analyzed in this retrospective study. We found that platelets, prothrombin activity, maximum oblique diameter of right hepatic lobe and spleen length were the independent predictors of liver cirrhosis in HCC patients. By cumulating the weight of risk scores of independent variables, we constructed the PPMS (PLT/PTA/maximum oblique diameter of right hepatic lob/spleen length) index. The areas under the receiver operating characteristic curves (AUROC) of PPMS index were 0.820, 0.667, and 0.650 in predicting ≥cirrhosis 1 (C1), ≥cirrhosis 2 (C2), and ≥cirrhosis 3 (C3), respectively. The optimal cut-off value of the PPMS index for predicting ≥C1, ≥C2, and ≥C3 was 4.392, 4.471, and 4.784, respectively. And the corresponding sensitivity was 63.1%, 63.2%, and 64.7%, the corresponding specificity was 89.4%, 64.3%, and 62.5%, respectively. Our study constructed a non-invasive liver cirrhosis index (PPMS) could distinguish patients from different stages of liver cirrhosis, which might add more preoperative information for HCC patients.

ASSESSMENT OF PHYTOCHEMICALS AND IN VITRO ANTIOXIDANT, ANTI-INFLAMMATORY ACTIVITY OF SARCOSTEMMA BRUNONIANUM WIGHT AND ARN

Objective: Sarcostemma brunonianum Wight and Arn is a potential medicinal plant belonging to Asclepiadaceae. Bioactive constituents of the plant support the application of treating various ailments in the traditional system of medicine. The study aims to determine the presence of various phytoconstituents in stem, root, and flowers. Methods: Hot percolation method was carried out to obtain crude extracts using different solvent systems from low polar-high polar solvents ranging from petroleum ether, chloroform, (mid-polar) ethyl acetate, methanol and water. Estimation of total phenols, tannins and In vitro antioxidant, anti-inflammatory activities were evaluated for the determination of potential pharmaceutical drugs. Results: The results revealed the presence of some phytoconstituents such as phenols, tannins, glycosides, gums and mucilages. Ascorbic acid, BSA, Rutin and Gallic acid were used as the reference standard. The total phenolic content was found to be high in stem methanol extract 440.84±69.99 mg/g Gallic acid equivalent, whereas the tannin content was 291.78±4.68 mg/g GAE. The result proves that the S. brunonianum stem methanol extract possesses antioxidant and anti-inflammatory activities when compared to reference standards. In vitro, Nitric oxide scavenging activity of stem showed a maximum % of inhibition in methanol stem extract (24.39µg/ml) and anti-inflammatory activity maximum inhibition was found to be (55.56 %) in stem methanol and flower(53.62 %). The IC50 (concentration required for 50% inhibition) was also calculated for the DPPH radical model. Conclusion: This study results proclaims and justifies the role of folklore medicinal plant S. brunonianum in the treatment of inflammatory-related ailments and can be recommended for an effective drug.

The correlation between the surface-active characteristics of SAFOL 23 – alcohol – water systems and the length of the alkyl radical of the alcohol

The effect of isobutyl and isoamyl alcohols on the surface-active characteristics of SAFOL 23 nonionic sur-factant was studied. The surface tension isotherms (STI) of an aqueous solution of surfactant and its water-alcohol compositions are obtained. The structure of mixed micelles and the values of the surfactant interac-tion factor in the micelle, based on the STIs of SAFOL 23 – alcohol – water systems, were calculated. The dependence of surface activity on the SAFOL 23: alcohol ratio passes through a maximum, which is associat-ed with the transition of alcohol from co-surfactant to co-solvent due to the increase in its quantity. The wet-ting process of high dispersed polytetrafluoroethylene (PTFE) by SAFOL 23 – alcohol – water compositions was studied, contact angle isotherms were constructed. The PTFE surface was hydrophilized by compositions at ratios which comply with surface activity maximum. SAFOL 23 is more adsorbed on the surface of the sol-id phase than on the liquid-gas interface. The appending of alcohol into an aqueous solution of surfactant changes the ratio between hydrophilic and lipophilic groups of the composition, which affects cloud point. It significantly expands the range of application of surfactants and allows the use of SAFOL 23 as a solubilizer, emulsifier and wetting agent.

Influence of Phosphodiesterase Inhibition on CRE- and EGR1-Dependent Transcription in a Mouse Hippocampal Cell Line

Signaling pathways, depending on the second messenger molecule cAMP, modulate hippocampal cell signaling via influencing transcription factors like cAMP-regulated element-binding protein (CREB) or early growth response 1 EGR1/Krox24/zif268/ZENK (EGR1). Here, we investigated two reporter cell lines derived from an immortalized hippocampal neuronal cell line stably expressing a CRE- or EGR1-luciferase reporter gene (HT22CREluc and HT22EGR1luc, respectively). The cells were subjected to phosphodiesterase inhibitors and other cAMP-modulating agents to investigate dose- and time-dependent phosphodiesterase (PDE)-mediated fine-tuning of cAMP-dependent transcriptional signaling. The non-isoform-specific cyclic nucleotide phosphodiesterase (PDE) inhibitor isobutyl-methyl-xanthine (IBMX), as well as selective inhibitors of PDE3 (milrinone) and PDE4 (rolipram), were tested for their ability to elevate CRE- and EGR1-luciferase activity. Pharmacological parameters like onset of activity, maximum activity, and offset of activity were determined. In summary, phosphodiesterase inhibition appeared similarly potent in comparison to adenylate cyclase stimulation or direct activation of protein kinase A (PKA) via specific cAMP agonists and was at least partly mediated by PKA as shown by the selective PKA inhibitor Rp-8-Br-cAMPS. Moreover, transcriptional activation by PDE inhibition was also influenced by organic anion-exchanger action and interacted with fibroblast growth factor (FGF) receptor-mediated pathways.

The large-scale magnetic field of Proxima Centauri near activity maximum

ABSTRACT We report the detection of a large-scale magnetic field at the surface of the slowly rotating fully convective (FC) M dwarf Proxima Centauri. 10 circular polarization spectra, collected from 2017 April to July with the HARPS-Pol spectropolarimeter, exhibit rotationally modulated Zeeman signatures suggesting a stellar rotation period of 89.8 ± 4.0 d. Using Zeeman–Doppler Imaging, we invert the circular polarization spectra into a surface distribution of the large-scale magnetic field. We find that Proxima Cen hosts a large-scale magnetic field of typical strength 200 G, whose topology is mainly poloidal, and moderately axisymmetric, featuring, in particular, a dipole component of 135 G tilted at 51° to the rotation axis. The large-scale magnetic flux is roughly 3× smaller than the flux measured from the Zeeman broadening of unpolarized lines, which suggests that the underlying dynamo is efficient at generating a magnetic field at the largest spatial scales. Our observations occur ∼1 yr after the maximum of the reported 7 yr-activity cycle of Proxima Cen, which opens the door for the first long-term study of how the large-scale field evolves with the magnetic cycle in an FC very low mass star. Finally, we find that Proxima Cen’s habitable zone planet, Proxima-b, is likely orbiting outside the Alfvèn surface, where no direct magnetic star–planet interactions occur.