Molecular networking-guided investigation of the secondary metabolome of four Morus species and their in vivo neuroprotective potential for the mitigation of Alzheimer's disease.

Alzheimer's Disease (AD) is a fatal age-related neurodegenerative condition with a multifactorial etiology contributing to 70% of dementia globally. The search for a multi-target agent to hit different targets involved in the pathogenesis of AD is crucial. In the present study, the neuroprotective effects of four Morus extracts were assessed in LPS-induced AD in mice. Among the studied species, M. macroura exhibited a profound effect on alleviating the loss of cognitive function, improved the learning ability, restored the acetylcholine esterase (AChE) levels to normal, and significantly reduced the tumor necrosis factor alpha (TNF-α) brain content in LPS-treated mice. To investigate the secondary metabolome of the studied Morus species, ultra-performance liquid chromatography coupled to tandem mass spectrometry (UPLC-HRMS/MS), aided with feature-based molecular networking, was employed. Among the annotated features, aryl benzofurans and prenylated flavonoids were suggested as being responsible for the observed neuroprotective effect. Furthermore, some of the detected metabolites were proposed as new natural products such as moranoline di-O-hexoside (1), isomers of trimethoxy-dihydrochalcone-O-dihexoside (59 & 76), (hydroxy-dimethoxyphenyl)butenone-O-hexoside (82), and O-methylpreglabridin-O-sulphate (105). In conclusion, our findings advocate the potential usage of M. macroura leaves for the management of AD, yet after considering further clinical trials.

Application of classification machine learning algorithms for characterizing nutrient transport in a clay plain agricultural watershed.

Excess nutrients in surface water and groundwater can lead to water quality deterioration in available water resources. Thus, the classification of nutrient concentrations in water resources has gained significant attention during recent decades. Machine learning (ML) algorithms are considered an efficient tool to describe nutrient loss from agricultural land to surface water and groundwater. Previous studies have applied regression and classification ML algorithms to predict nutrient concentrations in surface water and/or groundwater, or to categorize an output variable using a limited number of input variables. However, there have been no studies that examined the application of different ML classification algorithms in agricultural settings to classify various output variables using a wide range of input variables. In this study, twenty-four ML classification algorithms were implemented on a dataset from three locations within the Upper Parkhill watershed, an agricultural watershed in southern Ontario, Canada. Nutrient concentrations in surface water were classified using geochemical and physical water parameters of surface water and groundwater (e.g., pH), climate and field conditions as the input variables. The performance of these algorithms was evaluated using four evaluation metrics (e.g., classification accuracy) to identify the optimal algorithm for classifying the output variables. Ensemble bagged trees was found to be the optimal ML algorithm for classifying nitrate concentration in surface water (accuracy of 90.9%), while the weighted KNN was the most appropriate algorithm for categorizing the total phosphorus concentration (accuracy of 87%). The ensemble subspace discriminant algorithm gave the highest overall classification accuracy for the concentration of soluble reactive phosphorus and total dissolved phosphorus in surface water with an accuracy of 79.2% and 77.9%, respectively. This study exemplifies that ML algorithms can be used to signify exceedance of recommended concentrations of nutrients in surface waters in agricultural watersheds. Results are useful for decision makers to develop nutrient management strategies.

Non-penetrating deep sclerectomy versus combined trabeculotomy-trabeculectomy in primary congenital glaucoma.

Background: The primary mode of therapy in children with primary congenital glaucoma (PCG) and mild or no corneal edema is goniotomy, which has a high success rate. However, in developing countries, the diagnosis of PCG is usually delayed, and corneal cloudiness interferes with goniotomy. Therefore, trabeculotomy may be the best choice in such eyes. We compared the short-term efficacy and safety of primary combined trabeculotomy-trabeculectomy (primary CTT) with that of non-penetrating deep sclerectomy (NPDS) in managing PCG. Methods: This prospective, randomized, comparative study included patients with PCG referred to Al-Azhar University Hospitals within a 1-year period. Eyes were randomly allocated to one of two groups: eyes in NPDS group underwent NPDS, and those in primary CTT group underwent primary CTT. Baseline and frequent postoperative assessments of intraocular pressure (IOP), cup-to-disc ratio (C/D ratio), corneal diameter, and axial length were performed for up to 6 months. The success rates were recorded in both groups. Results: Forty eyes of 26 patients were included, with 20 eyes allocated to each group. The mean (standard deviation) age of all patients was 12.9 (9.5) months, with comparable ages and sex ratios between groups (both P > 0.05). Both groups demonstrated a significant reduction in IOP and C/D ratio at each postoperative visit compared to the baseline visit (all P < 0.001), with no significant difference detected between the groups (all P > 0.05), except for a significantly lower IOP in NPDS group at 1 month (P < 0.05). The corneal diameter and axial length were comparable between groups at baseline and remained unchanged at all postoperative visits (all P > 0.05). The groups had comparable success rates (P > 0.05). No serious complications were detected. Conclusions: CTT and NPDS both yielded reasonable IOP control and reversal of cupping in eyes with PCG. We observed equal effectiveness of the surgical procedures without major safety concerns. Further large-scale clinical trials with longer follow-up periods are needed to verify our preliminary findings.

A comparison between different management surgical approaches in the treatment of splenic flexure colon cancer

Background: There are many surgical approaches which described extent of resection of the colon for adequate surgicalmanagement of splenic flexure cancer, but up till now there is no established surgical procedure, this is because the presence of double lymphatic drainage of themesenteric vessels. Segmental resection of the colon for the management of splenic flexure cancer was a recently accepted surgical procedure. Objective: In the present study, we aimed to compare three surgical management techniques to clarify the best management approach of Egyptian patients with splenic flexure cancer regarding operative, clinical, and oncological outcomes: segmental resection, and extended left or right hemicolectomy,. Materials and Methods In the present study, we included 90 patients with splenic flexure cancer. Cases were divided into 3 groups. Each group included 30 patients in order to compare three surgical techniques: segmental resection, extended left hemicolectomy, and extended right hemicolectomy. Results: We have found no statistically significant differences between the three included groups regarding operative findings, postoperative complications, local recurrence, distant recurrence, disease progression, recurrence-free survival rate, progression-free survival rate, and overall survival rate. The operative time was longer, and the number of lymph nodes was higher in the extended right hemicolectomy group (p<0.001). Conclusion: We have shown that segmental resection of the splenic flexure is surgically and clinically suitable for the adequate management of operable cases of carcinoma of the splenic flexure. (AU)

The effect of wet-cupping therapy (hijama) in modulating autoimmune activity of Hashimoto's thyroiditis: A pilot controlled study.

OBJECTIVES: To investigate the possible effects of wet-cupping therapy (hijama) on autoimmune activity and thyroid hormonal profiles of Hashimoto's disease (HD) patients. METHODS: A prospective pilot controlled trial was carried out among adult females following HD at the Endocrinology Clinic of King Abdulaziz University Hospital, Jeddah, Saudi Arabia, from February 2014 until March 2017. A total of 13 patients (intervention group) underwent 3 hijama sessions at 3-week interval with a 6-month follow-up. Blood tests were carried out for both pre- and post-hijama, including: thyroid peroxidase antibody (TPO), thyroglobulin antibody (TG), thyroid stimulating hormone (TSH), thyroxine-4 (T4), and prolactin. Control group included 13 randomly selected HD patients following usual care with 2 consecutive measurements of TPO and TG at 2-3 months interval. RESULTS: Changes in anti-TPO and anti-TG showed a decrease in hijama group versus an increase in control group, and intervention group comparison was statistically significant. On a fixed thyroxine supplement for each patient, significant decrease in levels of anti-TPO, anti-TG, TSH, prolactin, and erythrocyte sedi-mentation rate (ESR) occurred. CONCLUSION: These findings are presumptive to the efficacy of hijama on the pathogenesis of HD in modulating the immune inflammatory process demonstrated by the reduction in ESR, TPO, and TSH levels on a fixed thyroxin supplementation dose, along with patient-reported clinical improvement and positive changes in ultrasound including regaining of gland physiological size, echogenicity, and vascularity.

Modulatory role of garlic ( Allium sativum) extract against cisplatin- induced nephrotoxicity in female albino rats and their offspring.

Background: Cisplatin (CP) is one of the chemotherapeutic drugs widely utilized in the treatment of several malignancies. However, recently; its use has been limited because of its hazardous health drawbacks. Previous researches confirmed that CP has severe deleterious side effects on pregnant mothers and their fetuses. Garlic ( Allium sativum) extract has been claimed to exhibit potent antioxidative and free radical scavenging abilities. Aim: This work is mainly designed to evaluate the potential therapeutic role of garlic extract against CP-induced nephrotoxicity in pregnant rats and their offspring. Methods: 24 pregnant rats were used in the current study. They were randomly allocated into four groups (n=6):  control, garlic, CP, and CP + garlic group. At the end of the weaning period, the mothers and the offsprings of all groups were sacrificed, the kidneys were immediately excised, and processed for histological and biochemical investigations. Also, blood samples were withdrawn and processed for estimation of the assigned biochemical parameters.   Results: The renal histological sections from CP-treated mother rats displayed pronounced histopathological lesions however, their offspring showed mild renal histopathological lesions if compared with those of their mothers. The levels of renal tissue Superoxide dismutase, catalase, and glutathione peroxidase enzymes were significantly decreased. On the contrary, the levels of malondialdehyde, serum urea, and creatinine were significantly increased in CP-treated mother rats and their offspring as compared with control. The percentage value of caspase 3 activity was markedly elevated in the renal tissues of CP-treated mother rats and their offspring compared to the control group. Supplementation of garlic extract to the CP treated rats; the overall histological lesions, as well as biochemical parameters, were restored nearly to the control ones. It is concluded that garlic ( Allium sativum) extract has a powerful ameliorative role against CP-induced nephrotoxicity in pregnant rats and their offspring.

Silver nanoparticles from insect wing extract: Biosynthesis and evaluation for antioxidant and antimicrobial potential.

Silver nanoparticles (AgNPs) are among the most widely synthesized and used nanoparticles (NPs). AgNPs have been traditionally synthesized from plant extracts, cobwebs, microorganisms, etc. However, their synthesis from wing extracts of common insect; Mang mao which is abundantly available in most of the Asian countries has not been explored yet. We report the synthesis of AgNPs from M. mao wings extract and its antioxidant and antimicrobial activity. The synthesized AgNPs were spherical, 40-60 nm in size and revealed strong absorption plasmon band around at 430 nm. Highly crystalline nature of these particles as determined by Energy-dispersive X-ray analysis and X-ray diffraction further confirmed the presence of AgNPs. Hydrodynamic size and zeta potential of AgNPs were observed to be 43.9 nm and -7.12 mV, respectively. Fourier-transform infrared spectroscopy analysis revealed the presence of characteristic amide proteins and aromatic functional groups. Thin-layer chromatography (TLC) and Gas chromatography-mass spectroscopy (GC-MS) analysis revealed the presence of fatty acids in the wings extract that may be responsible for biosynthesis and stabilization of AgNPs. Further, SDS-PAGE of the insect wing extract protein showed the molecular weight of 49 kDa. M. mao silver nanoparticles (MMAgNPs) exhibit strong antioxidant, broad-range antibacterial and antifungal activities, (66.8 to 87.0%), broad-range antibacterial and antifungal activities was found with maximum zone of inhibition against Staphylococcus aureus MTCC 96 (35±0.4 mm) and Fusarium oxysporum f. sp. ricini (86.6±0.4) which signifies their biomedical and agricultural potential.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Short-Term Outcome and MRI Changes in Three Adult Patients with Sickle Cell Disease and Aseptic Osteonecrosis after Treatment with Hyperbaric Oxygen Therapy: A Preliminary Report.

BACKGROUND: Musculoskeletal manifestations are common in sickle cell disease (SCD). Vaso-occlusive crisis can manifest acutely as joint and bone pain, osteomyelitis and/or arthritis. It can also lead to chronic bone aches, bone deformities, degenerative arthritis, pathological fractures, and osteoporosis. Hyperbaric oxygen (HBO) therapy is a mode of treatment in which the patient is exposed to very high arterial and tissue oxygen pressure, during multiple sessions. It has been used as primary or adjunctive therapy for a variety of medical disorders, including necrotizing infection and sickle cell crisis. CASE REPORT: In this case series, 3 patients with SCD and avascular necrosis were treated with 15-40 sessions of HBO and were assessed 6-12 months by MRI after treatment. They showed different clinical outcomes and MRI changes. CONCLUSION: We concluded that HBO can result in some subjective improvement, especially in early stages. Further studies on severe cases are needed.

Bio-redox potential of Hyphaene thebaica in bio-fabrication of ultrafine maghemite phase iron oxide nanoparticles (Fe2O3 NPs) for therapeutic applications.

Maghemite (Fe2O3-NPs) nanoparticles were synthesized by a convenient, green and cost effective method using aqueous fruit extracts of Hyphaene thebaica. Different techniques like FTIR, XRD, UV-Vis, Raman, HR-TEM, EDS. SAED, Zeta potential were used to establish the nature of Fe2O3-NPs, while the therapeutic properties were studied using different biological assays including antiviral, antibacterial, antifungal, antioxidant and enzyme inhibition assays. XRD pattern revealed sharp peaks and a crystalline nature of Fe2O3-NPs. HR-TEM revealed quasi-spherical and cuboidal morphologies, while the particle size in ~10 nm. FTIR indicated a sharp peak centered at ~444 cm-1 which is the characteristic FeO band vibration. SAED pattern indicated the crystalline nature while EDS also confirmed the synthesis of Fe2O3 NPs. Zeta potential was obtained in different solvents and physiological buffers indicating highest value in water (-26.5 mV) and lowest in DMSO (-15.8 mV). Tested bacterial strains, Bacillus subtilis was found to be inhibited significantly. Aspergillus flavus appeared to be susceptible to all of the tested concentration of Fe2O3 NPs. Maximum 40.78% FRSA was obtained at 400 µg/mL. Cell culture based studies on RD cells and L20B cells indicated reduction in viability of cells with increase concentration of Fe2O3 NPs. Moderate inhibition of polio virus-1 and polio virus-2 was observed, after culturing the virus in the L20B cells. Excellent Protein Kinase (PK) inhibition was revealed. Hemolytic potential and cytotoxic potential was indicated to be dose dependent. In conclusion, the present report for the first time reports the synthesis of Fe2O3 NPs from H. thebaica fruits and reveals their biomedical potential including antiviral potential.

Accuracy of American College of Surgeons National Surgical Quality Improvement Program Universal Surgical Risk Calculator in Predicting Complications Following Robot-Assisted Radical Cystectomy at a National Comprehensive Cancer Center.

Introduction: There is paucity of literature about the validation of the American College of Surgeons National Surgical Quality Improvement Program (ACS NSQIP®) surgical risk calculator for prediction of outcomes after robot-assisted radical cystectomy (RARC). We sought to evaluate the accuracy of the ACS NSQIP surgical risk calculator in the patients who underwent RARC at our institute. Methods: We retrospectively reviewed our prospectively maintained database for patients who underwent RARC between 2005 and 2017. Accuracy of the ACS NSQIP surgical risk calculator was assessed, by comparing the rate of actual complication events after surgery with the receiver operating characteristics curve analysis by calculating the fractional area under the curve (AUC) and the Brier score (BS). We utilized the code number 51595 and 51596 in the ACS NSQIP calculator for the patients undergoing radical cystectomy and reconstructed with the ileal conduit and neobladder, respectively. Results: A total of 462 patients were included in this study: 99 (22%) had diabetes, 302 (66%) had hypertension requiring medication, and 241 (52%) were classified as high American Society of Anesthesiologists (≥3) class. The actual observed rates of any complication and serious complications were 48% and 11%, vs 29% and 25% predicted by the ACS NSQIP, respectively. The actual mean length of hospital stay (10.6 ± 7.8 days) was longer compared with the predicted length (8.5 ± 1.6 days). AUC values were low and the BSs were high for any complication (AUC: 0.50 and BS: 0.29), serious complication (AUC: 0.53 and BS: 0.12), urinary tract infection (AUC: 0.61 and BS: 0.14), renal insufficiency (AUC: 0.64 and BS: 0.08), return to operation room (AUC: 0.58 and BS: 0.07), and early readmission (AUC: 0.55 and BS: 0.11, respectively). Conclusions: The ACS NSQIP calculator demonstrated low accuracy in predicting postoperative outcomes after RARC. These findings highlight the need for development of procedure- and technique-specific RARC calculators.

Eco-friendly synthesis, characterization, in vitro and in vivo anti-inflammatory activity of silver nanoparticle-mediated Selaginella myosurus aqueous extract.

INTRODUCTION: There is emerging interest in medicinal plants in the biomedical field, due to their multitude of chemicals which show anti-inflammatory, antimicrobial, antiviral, or antitumoral potential. Research on medicinal plants has shown that nanotechnology could offer new solutions in the quality control, delivery aspects, or in sustaining herbal biological activities. This work reports on the preparation and characterization of silver nanoparticle-mediated Selaginella myosurus plant extract. METHODS: Ultraviolet-visible spectroscopy, Fourier transform infrared spectroscopy, powder X-ray diffraction, energy dispersive X-ray spectroscopy, high-resolution scanning electron microscopy, high-resolution transmission electron microscopy, and selected area electron diffraction have been used to characterize the prepared silver nanoparticles. The synthetic stability was studied by varying concentrations and pH of reactants. Egg albumin denaturation and carrageenan-induced rat paw edema model were used to ascertain the anti-inflammation. RESULTS: Ultraviolet-visible spectroscopy gave plasmon resonance ranging between 420 and 480 nm while Fourier transform infrared spectroscopy proved nano interface functionalized with organics. The powder X-ray diffraction pattern is in agreement with silver and silver chloride nanoparticles of crystallite size 33.7 nm and 44.2 nm for silver and silver chloride, respectively. Energy dispersive X-ray spectroscopy enables elemental characterization of the particles consisting of silver and silver chloride among main elements. Spherical silver grain of 58.81 nm average size has been depicted with high-resolution scanning electron microscopy and high-resolution transmission electron microscopy. Inhibitions of 99% and 60% were obtained in vitro and in vivo, respectively. CONCLUSION: The albumin denaturation and carrageenan-induced rat hind paw edema model to assess the anti-inflammatory potential of generated nanoparticles suggests that the silver nanoparticles may act as reducing/inhibiting agents on the release of acute inflammatory mediators. Hence, this work clearly demonstrated that silver nanoparticles mediated-Selaginella myosurus could be considered as a potential source for anti-inflammatory drugs.

In vitro Evaluation of Cytotoxic Activities of Essential Oil from Moringa oleifera Seeds on HeLa, HepG2, MCF-7, CACO-2 and L929 Cell Lines.

Moringa oleifera Lam. (Moringaceae) is widely consumed in tropical and subtropical regions for their valuable nutritional and medicinal characteristics. Recently, extensive research has been conducted on leaf extracts of M. oleifera to evaluate their potential cytotoxic effects. However, with the exception of antimicrobial and antioxidant activities, little information is present on the cytotoxic activity of the essential oil obtained from M. oleifera seeds. Therefore, the present investigation was designed to investigate the potential cytotoxic activity of seed essential oil obtained from M. oleifera on HeLa, HepG2, MCF-7, CACO-2 and L929 cell lines. The different cell lines were subjected to increasing oil concentrations ranging from 0.15 to 1 mg/mL for 24h, and the cytotoxicity was assessed using MTT assay. All treated cell lines showed a significant reduction in cell viability in response to the increasing oil concentration. Moreover, the reduction depended on the cell line as well as the oil concentration applied. Additionally, HeLa cells were the most affected cells followed by HepG2, MCF-7, L929 and CACO-2, where the percentages of cell toxicity recorded were 76.1, 65.1, 59.5, 57.0 and 49.7%, respectively. Furthermore, the IC50 values obtained for MCF-7, HeLa and HepG2 cells were 226.1, 422.8 and 751.9 µg/mL, respectively. Conclusively, the present investigation provides preliminary results which suggest that seed essential oil from M. oleifera has potent cytotoxic activities against cancer cell lines.

Apomixis in different ploidy levels of cassava.

Two polyploid hybrids between cassava (Manihot esculenta) cultivar 307-2 and its wild relatives M. glaziovii and M. anomala, were studied to examine the relationship between ploidy level and the production of seeds without fertilization. A clearing method was applied to assess ovule sizes as an indication of multiembryony. The diploid cultivar 307-2 had regular 18 bivalents at meiotic metaphase 1 while the polyploid types showed chromosome configurations varying from 3 to 4 quadrivalents and 28 to 30 bivalents. A total of 14% of studied ovules of the polyploid hybrid involving M. glaziovii were multiebryonic, while the percentage of multiembryony was as low as 2% in the polyploid hybrid M. anomala×M. esculenta. Diploid hybrid types did not show any multi embryony. Adventitious embryos were found and documented for the first time in polyploid hybrids M. esculenta×M. glaziovii. The association of multiple embryo formation with ovary size and pollination showed that apomictic embryos form independently from fertilization. Simple iodized carmine stain for measuring pollen viability proved as efficient as the sophisticated Alexander method.