Crateva nurvala stem bark is commonly used in Ayruveda in treatment of many renal injuries, e.g., urinary lithiasis, diuretic and nephroprotective. However, its protective effect against renal ...ischaemia/reperfusion, the major cause of acute kidney injury, has never been studied. Moreover, no comprehensive chemical profiling of its extracts was recorded.
Assessment of the protective effect of the plant extracts against renal ischaemia/reperfusion and elucidation of the possible mechanism of action. Then, to determine its bioactive constituents using modern UPLC-HRMS technique.
Unilateral ischaemia was induced by clamping the left renal artery for 1h then reperfusion for 24h. Rats were divided in 4 groups: i) sham-operated group, ii) ischaemia/reperfusion, I/R group, iii) I/R protected by previous administration of Crateva leaves extract, CLE group and iv) I/R protected by previous administration of Crateva bark extract, CBE group. At the end of reperfusion, blood samples were analyzed for renal function biomarkers. Kidneys were examined histopathologically and their homogenates were used in determining the intracellular levels of oxidative stress, inflammatory, and apoptosis markers.
Leaves and bark extracts attenuated the deleterious effects of I/R apparent in reducing LDH, creatinine and blood urea nitrogen levels. The extracts reduced the oxidative stress by replenishing the glutathione levels and Nrf2 factor levels. Moreover, extracts decreased levels of pro-inflammatory TNF-α, NF-κβ and IL-6; which ultimately resulted in reducing the pro-apoptotic caspase-3.
Bark and leave extracts have quite similar chemical profile where 42 compounds of various chemical classes were identified. Flavonoids are the major class of the bioactive phytochemicals
C. nurvala extracts had effectively ameliorated the deleterious effects of renal I/R by mainly counteracting oxidative stress and presumably inflammation. Consequently, it can be used as a complementary treatment with other agents. In this aspect, leaves stand as a sustainable alternative to bark. The presented chemical profiling can be used in future standardization and quality control of the drug.
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The sequence of the biosynthetic steps leading from 3,5-dihydroxybiphenyl to aucuparin was elucidated using cell-free extracts and microsomes.
•3,5-Dihydroxybiphenyl is the precursor of both the ...biphenyl phytoalexin aucuparin and the dibenzofuran phytoalexin eriobofuran.•The sequence of the biosynthetic steps leading to formation of aucuparin is O-methylation – 4-hydroxylation – O-methylation.•The two alkylation reactions are catalyzed by distinct methyltransferases.•4-Hydroxylase is a microsomal cytochrome P450 monooxygenase.
Aucuparin is the most widely distributed biphenyl phytoalexin in the rosaceous subtribe Pyrinae, which includes the economically important fruit trees apple and pear. The biphenyl scaffold is formed by biphenyl synthase, which catalyzes biosynthesis of 3,5-dihydroxybiphenyl. Conversion of this precursor to aucuparin (3,5-dimethoxy-4-hydroxybiphenyl) was studied in cell cultures of Sorbus aucuparia after treatment with an elicitor preparation from the scab-causing fungus Venturia inaequalis. The sequence of the biosynthetic steps detected was O-methylation – 4-hydroxylation – O-methylation. The two alkylation reactions were catalyzed by distinct methyltransferases, which differed in pH and temperature optima as well as stability. Biphenyl 4-hydroxylase was a microsomal cytochrome P450 monooxygenase, whose activity was appreciably decreased by the addition of established P450 inhibitors. When fed to V. inaequalis-treated S. aucuparia cell cultures, radioactively labeled 3,5-dihydroxybiphenyl was not only incorporated into aucuparin but also into the dibenzofuran eriobofuran, the accumulation of which paralleled that of aucuparin. However, biphenyl 2′-hydroxylase activity proposed to be involved in dibenzofuran formation was detected in neither microsomes nor cell-free extracts in the presence of NADPH and 2-oxoglutarate, respectively. Nevertheless, a basis for studying biphenyl biosynthesis at the gene level is provided.
Fire blight is a devastating disease of Rosaceae plants, such as apple and pear trees. It is characterized by necrosis of plant tissue, caused by the phytopathogenic bacterium Erwinia amylovora. The ...plant pathogen produces the well‐known antimetabolite 6‐thioguanine (6TG), which plays a key role in fire blight pathogenesis. Here we report that YcfR, a member of the LTTR family, is a major regulator of 6TG biosynthesis in E. amylovora. Inactivation of the regulator gene (ycfR) led to dramatically decreased 6TG production. Infection assays with apple plants (Malus domestica cultivar Holsteiner Cox) and cell cultures of Sorbus aucuparia (mountain ash, rowan) revealed abortive fire blight pathogenesis and reduced plant response (biphenyl and dibenzofuran phytoalexin production). In the presence of the ΔycfR mutant, apple trees were capable of activating the abscission machinery to remove infected tissue. In addition to unveiling the regulation of 6TG biosynthesis in a major plant pathogen, we demonstrate for the first time that this antimetabolite plays a pivotal role in dysregulating the plant response to infection.
Blight relief: Analysis of the regulation of 6‐thioguanine (6TG) biosynthesis in the pathogen Erwinia amylovora sheds new light on the pathogenesis of fire blight. Surprisingly, at low 6TG titers, apple trees are capable of activating the abscission machinery to excise infected tissue and to dam further pathogen dissemination, thus preventing full infection of the tree.
The current study aims to investigate the effects of swell pressure on the bearing capacity of swelling soil. A model and some laboratory tests have been created to investigate the swell pressure ...effect on the bearing capacity variation of soil swelling due to swelling pressure. The influence of varying water content
and dry unit weight (γ
) on the shear strength and swelling pressure was studied. The soil has been taken from Diwan Residential Compound-Mosul. It is classified as highly swelling soil. The swell pressure of soils at their natural water content reached
/
. Experiment results show that the parameters of shear resistance decreased with the
increase at the constant value of (γ
), increased with the (
) increase when the
was constant. Results show that the swelling pressure decreased with the
increase, while it increased with the (γ
) increase. Also, the results obtained using was model show that the resistance of bearing capacity of pre-saturated selected soil was
/
, while the bearing capacity was
/
when taking into account in the generation of swelling pressure.
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•We designed and synthesized some new dispiropyrrolodinyl-oxindole -based alkaloids.•We evaluated the newly synthesized analogues as cholinesterase inhibitors.•Some of the new ...chemical entities showed promising BuChE inhibitors.•The bio-results were validated by 2D-QSAR study.•The achieved model can be adopted for optimizing hits of high potency.
In this work, we describe the regioselective synthesis of some new dispiroindene-2,3′-pyrrolidine-2′,3″-indoline-1,2″(3H)-dione 4-29 attributable to the previously described methods. All the new chemical entities were assessed in-vitro as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes; while no significant inhibitory activity for the tested compounds were assigned on AChE, compounds 4, 27, 29, 28 and 15 were the most active against BChE enzyme with IC50 = 13.7 µM, 21.8 µM, 22.1 µM, 22.9 µM and 24.9 µM respectively compared to Donepezil (IC50 = 0.72 µM). Compound 4 was found to have a mixed type mode of inhibition, the bioactivity of the new chemical entities (N = 26, n = 5, R2 = 0.893, R2 cvOO = 0.831, R2 cvMO = 0.838, F = 33.32, s2 = 0.003) was elucidated via a statistically significant QSAR model utilizing CODESSA-Pro software that validated the observed results.
Biphenyl and dibenzofuran phytoalexins were detected in the transition zones of fire blight-infected stems of apple and pear and tested for antibacterial activity against Erwinia amylovora. Display ...omitted
► Fire blight-infected apple and pear shoots form biphenyls and dibenzofurans. ► The exclusive accumulation site is the transition zone of stems. ► Leaves are devoid of phytoalexins. ► 3,5-Dihydroxybiphenyl exhibits strong antibacterial activity against Erwinia amylovora.
In the rosaceous subtribe Pyrinae (formerly subfamily Maloideae), pathogen attack leads to formation of biphenyls and dibenzofurans. Accumulation of these phytoalexins was studied in greenhouse-grown grafted shoots of Malus domestica cv. ‘Holsteiner Cox’ and Pyrus communis cv. ‘Conference’ after inoculation with the fire blight bacterium, Erwinia amylovora. No phytoalexins were found in leaves. However, both classes of defence compounds were detected in the transition zone of stems. The flanking stem segments above and below this zone, which were necrotic and healthy, respectively, were devoid of detectable phytoalexins. The transition zone of apple stems contained the biphenyls 3-hydroxy-5-methoxyaucuparin, aucuparin, noraucuparin and 2′-hydroxyaucuparin and the dibenzofurans eriobofuran and noreriobofuran. In pear, aucuparin, 2′-hydroxyaucuparin, noreriobofuran and in addition 3,4,5-trimethoxybiphenyl were detected. The total phytoalexin content in the transition zone of pear was 25 times lower than that in apple. Leaves and stems of mock-inoculated apple and pear shoots lacked phytoalexins. A number of biphenyls and dibenzofurans were tested for their in vitro antibacterial activity against some Erwinia amylovora strains. The most efficient compound was 3,5-dihydroxybiphenyl (MIC=115μg/ml), the immediate product of biphenyl synthase which initiates phytoalexin biosynthesis.
Fatty liver injury is a prevalent condition in most farmed fish, yet the molecular mechanisms underpinning this pathology remain largely elusive. A comprehensive feeding trial spanning eight weeks ...was conducted to discern the potential of dietary chitosan in mitigating the deleterious effects of a high-fat diet (HFD) while concurrently exploring the underlying mechanism. Growth performance, haemato-biochemical capacity, antioxidant capacity, apoptotic/anti-apoptotic gene expression, inflammatory gene expression, and histopathological changes in the liver, kidney, and intestine were meticulously assessed in Nile tilapia. Six experimental diets were formulated with varying concentrations of chitosan. The first three groups were administered a diet comprising 6% fat with chitosan concentrations of 0%, 5%, and 10% and were designated as F6Ch0, F6Ch5, and F6Ch10, respectively. Conversely, the fourth, fifth, and sixth groups were fed a diet containing 12% fat with chitosan concentrations of 0%, 5%, and 10%, respectively, for 60 days and were termed F12Ch0, F12Ch5, and F12Ch10. The results showed that fish fed an HFD demonstrated enhanced growth rates and a significant accumulation of fat in the perivisceral tissue, accompanied by markedly elevated serum hepatic injury biomarkers and serum lipid levels, along with upregulation of pro-apoptotic and inflammatory markers. In stark contrast, the expression levels of nrf2, sod, gpx, and bcl-2 were notably decreased when compared with the control normal fat group. These observations were accompanied by marked diffuse hepatic steatosis, diffuse tubular damage, and shortened intestinal villi. Intriguingly, chitosan supplementation effectively mitigated the aforementioned findings and alleviated intestinal injury by upregulating the expression of tight junction-related genes. It could be concluded that dietary chitosan alleviates the adverse impacts of an HFD on the liver, kidney, and intestine by modulating the impaired antioxidant defense system, inflammation, and apoptosis through the variation in nrf2 and cox2 signaling pathways.
Evidently, complementary and alternative medicine (CAM) is a recognized medical practice that efficiently uses multiple treatment therapies and techniques in the prevention and management of a ...variety of human disorders. Many medical schools have integrated CAM curriculum in medical education system worldwide. Research in knowledge, attitude, and practice (KAP) of diverse health professionals exposed to CAM courses is important from many perspectives including improvement in KAP and teaching skills of faculty, together with capacity building and curriculum development.
This pre- and post-design cross-sectional study aimed to assess CAM-KAP of two intakes of medical students in Majmaah University, Saudi Arabia.
The second-year medical students of the first (year 2012-2013) and second (year 2013-2014) intake (n=26 and 39, respectively) were selected for this study. A reliable, 16-item self-administered questionnaire was distributed among all the students for answering before and after the 48-hour CAM course. The data were analyzed using appropriate statistical test of significance.
Medical students' knowledge and attitude toward CAM significantly improved across some subitems of CAM questionnaire with a positive trend in the rest of its items including their views on CAM practices.
CAM course tends to have a positive impact on KAP of medical students. The preliminary results of this study call for further research with a larger sample in academic settings across the nation.
PurposeThis study aims to assess the combination of anterior lamellar recession (ALR) with blepharoplasty, suprasternal fixation, and internal eyelash bulb extirpation of aberrant lashes posteriorly ...located in patients with any grade of upper eyelid trachomatous cicatricial entropion. Patients and MethodsWe reviewed the clinical data of eighty-six patients (143 eyelids) including age, gender, systemic medical illnesses, and comprehensive ophthalmological assessment. Eyelid evaluation was recorded, including laterality, previous surgical technique used, possible trichiasis etiology, abnormality of the lid margin, tarsal plate consistency (shrinkage or loosening), skin fold overhanging, laxity of the pretarsal skin, margin reflex distance 1 (MRD1), lagophthalmos, and lid retraction. The success rate was assessed at 3, 6, 9, and 12 months postoperative. ResultsThe success rate was 97.2% in the third month, which decreased significantly to 92.3% in the 6th month and 90.2% in the 9th month (P = 0.01, and 0.001 respectively). In the 9th month, we had fourteen failed cases. All of them were submitted for a second intervention. Three underwent electrolysis, four cases underwent re-internal bulb extirpation, four cases underwent the same procedure, and three cases underwent epilation. The success of the failed cases after the second intervention was significantly associated with the type of reintervention (P = 0.03), in which all of them succeed except two cases that underwent epilation. Kaplan-Meier analysis showed that the mean recurrence time in our study was 6.8 months (95% CI = 5.8-7.7 months). ConclusionThis study showed the combination of ALR with blepharoplasty, suprasternal fixation, and cauterization or internal bulb extirpation of posteriorly located lashes procedure resulted in a high success rate in patients with any form of UCE with no increase in incidence or degree of lagophthalmos associated with UCE.
A new polydentate Schiff base ligand and its metal complexes were synthesized and characterized by elemental analyses, IR, 1H NMR, electronic, ESR and mass spectra, conductivity and magnetic ...susceptibility measurements as well as thermal analyses. The free ligand was synthesized by condensation of o-acetoacetylphenol with salicylaldehyde hydrazone. The analytical and spectroscopic tools showed that the obtained complexes are mono- and binuclear complexes, which can be generally formulated as: (L)M2X2(H2O)m·nZ; M = Cr, Fe, Ni or Cu, X = OAc or NO3, m = 5 or nil and n = 3, 1.5 or 0.5 and Z = EtOH or H2O, (H2L)2M(X)m.nH2O; M = Mn, Zn, or Cd, X = EtOH, H2O or nil, m = 2 or nil and n = 3.5 or 0, (HL)2Co2·0.5H2O and (H2L)2UO2(H2O). The metal complexes displayed octahedral, tetrahedral and square-planar geometrical arrangements, while uranium complex displayed seven-coordinate. Kinetic parameters (Ea, A, ΔH, ΔS and ΔG) of the thermal decomposition stages have been evaluated using Coats–Redfern equations. The molecular structural parameters of the ligand and its metal complexes have been calculated and correlated with the experimental data such as IR. The antimicrobial activity of the ligand and its complexes was screened against some kinds of bacteria and fungi. The antitumor activity of the ligand and its Ni(II) and Cu(II) complexes was investigated against HepG2 cell line.
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•A new Schiff base and its metal complexes were synthesized and characterized.•The complexes exhibited different geometrical arrangements.•Kinetic parameters were calculated.•The ligand and its complexes showed antimicrobial activity.•The antitumor activity of the ligand and its Ni(II) and Cu(II) complexes was investigated against HepG2 cell line.
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