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Ethnopharmacological Relevance: Hypericum roeperianum is a medicinal spice traditionally used in West Africa to treat female sterility, fungal infections, and cancer. It has previously been reported that H. roeperianum exhibits cytotoxic potential by reducing the viability of cancer cells involving multidrug-resistant phenotypes, but its underlying molecular mechanism remains unknown., Aim of the Study: The mechanistic involvement of H. roeperianum methanolic crude extract (HRC) in attenuating breast cancer progression by exploring the effects on mitochondrial apoptosis and epithelial-mesenchymal transition (EMT) was investigated., Materials and Methods: In the present study, we examined the anticancer properties of HRC through MTT assay, colony formation, wound healing assay, spheroid formation, DNA fragmentation and flow cytometry for cell cycle arrest, apoptosis (Annexin V/PI staining) and mitochondrial membrane potential (MMP) (JC-1) detection. In addition, western blot analysis of various proteins and quantitative real time PCR of various genes involved in apoptosis, EMT and the PI3K/Akt/mToR signal transduction pathway were performed., Results: This study revealed that HRC treatment significantly decreased breast cancer cell viability, colony forming efficiency and reduced the ability of cell migration and spheroid formation. HRC also induced apoptosis in MDA-MB-231 and MCF-7 via promoting G0/G1 cell cycle arrest, disruption of mitochondrial membrane potential and induction of DNA damage. The crude extract induced apoptosis by activating the intrinsic pathway with a stronger effect that relies on the combined potency of associated molecular markers including Bax, Bad, Bcl-2, cytochrome C, caspase-9, and cleaved-PARP. It was also found that HRC regulates the PI3K/Akt/mToR pathway. In addition, HRC inhibited EMT by expressional alteration of Vimentin and E-cadherin, as well as the regulatory transcription factors such as Snail and Slug. The in vitro findings reflected similar mechanistic approach in 4T1 cell induced syngeneic mice model, indicating the reduction of tumor volume along with the significant expressional alteration of EMT and apoptotic markers., Conclusion: Taken together the findings concluded that H. roeperianum is a potential source of cytotoxic phytochemicals that exhibit abortifacient effect on breast cancer, both in vitro and in vivo, thus could further be utilized in breast cancer therapy., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Chemical investigation of the methanol extract from the leaves of H. roeperianum led to the isolation of a new tetraoxygenated xanthone along with eleven known compounds including six xanthones, one polyketide, one flavonoid, one ferulic acid derivative and two pentacyclic triterpenoids. Their structures were established on the basis of 1D- and 2D-NMR, UV, IR, and MS experiments, and by comparison of their spectroscopic data with those of similar compounds reported in the literature. The new xanthone was tested against a panel of eight bacterial strains including six Gram-negative and two Gram-positive bacteria. As results, it exhibited weak antibacterial activity with MIC values ranging from 64 to 128 µg/mL.

Purpose: Z-spectrum imaging, defined as the consecutive collection of images after saturating over a range of frequency offsets, has been recently proposed as a method to measure the fat-water fraction by the simultaneous detection of fat and water resonances. By incorporating a binomial pulse irradiated at each offset before the readout, the spectral selectivity of the sequence can be further amplified, making it possible to monitor the subtle proton resonance frequency shift that follows a change in temperature., Methods: We tested the hypothesis in aqueous and cream phantoms and in healthy mice, all under thermal challenge. The binomial module consisted of 2 sinc-shaped pulses of opposite phase separated by a delay. Such a delay served to spread out off-resonance spins, with the resulting excitation profile being a periodic function of the delay and the chemical shift., Results: During heating experiments, the water resonance shifted downfield, and by fitting the curve to a sine function it was possible to quantify the change in temperature. Results from Z-spectrum imaging correlated linearly with data from conventional MRI techniques like T 1 mapping and phase differences from spoiled GRE., Conclusion: Because the measurement is performed solely on magnitude images, the technique is independent of phase artifacts and is therefore applicable in mixed tissues (e.g., fat). We showed that Z-spectrum imaging can deliver reliable temperature change measurement in both muscular and fatty tissues., (© 2021 International Society for Magnetic Resonance in Medicine.)

Ethnopharmacological Relevance: Infections due to multidrug-resistant (MDR) bacteria constitute a real problem in the public health worldwide. Hypericum roeperianum Schimp. ex A. Rich (Hypericaceae) is used traditionally for treatment of various ailments such as abdominal pains, constipation, diarrhea, indigestion, nausea, and bacterial diseases., Aim of the Study: This study was aimed at investigating the antibacterial and antibiotic-modifying activity of the crude methanol extracts (HRB), ethyl-acetate soluble fraction (HRBa), residual material (HRBb), and 11 compounds from the bark of Hypericum roeperianum against multi-drug resistant (MDR) bacteria expressing active efflux pumps., Materials and Methods: The antibacterial activity, the efflux pump effect using the efflux pump inhibitor (EPI), phenylalanine-arginine-ß-naphthylamide (PAβN), as well as the antibiotic-modifying activity of samples were determined using the broth micro-dilution method. Spectrophotometric methods were used to evaluate the effects of HRB and 8,8-bis(dihydroconiferyl) diferulate (11) on bacterial growth, and bacterial membrane damage, whereas follow-up of the acidification of the bacterial culture was used to study their effects on bacteria proton-ATPase pumps., Results: The crude extract (HRB), HRBa, and HRBb had selective antibacterial activity with MICs ranging from 16 to 512 μg/mL. Phytochemical 11 displayed the best antibacterial activity (0.5 ≤ MIC ≤ 2 μg/mL). The activity of HRB and 11 in the presence of EPI significantly increased on the tested bacteria strains (up to 32-fold). The activity of cloxacillin (CLO), doxycycline (DOX), and tetracycline (TET), was considerably improved (up to 64-fold) towards the multidrug-resistant Enterobacter aerogenes EA-CM64 strain. The crude extract (HRB) and 11 induced the leakage of bacterial intracellular components and inhibited the proton-ATPase pumps., Conclusions: The crude extract (HRB) and 8,8-bis(dihydroconiferyl)diferulate from the bark of Hypericum roeperianum are good antibacterial candidates that deserve further investigations to achieve antibacterial drugs to fight infections involving MDR bacteria., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The main objective of the study was to determine if rodent housing conditions, specifically housing climate, could impact the in vivo performance of poly(lactide-co-glycolide) (PLGA) microspheres through temperature modification of the subcutaneous space. Vivitrol®, a once monthly naltrexone injectable suspension, was chosen as a model PLGA microparticle formulation for this study. Two lots of Vivitrol were used to ascertain any potential differences that may exist between the batches and if in vitro characterization techniques could delineate any variation(s). The pharmacokinetics of the naltrexone-PLGA microparticles were determined in the rodent model under two different housing climates (20 vs. 25 °C). The results demonstrate that such difference in housing temperature resulted in a change in subcutaneous temperature but actually within a narrow range (36.31-36.77 °C) and thus minimally influenced the in vivo performance of subcutaneously injected microparticles. The shake-flask method was used to characterize the in vitro release at 35, 36, and 37 °C and demonstrated significant differences in the in vitro release profiles across this range of temperatures. Minimal differences in the in vitro characterization of the two lots were found. While these results did not provide statistical significance, the local in vivo temperature may be a parameter that should be considered when evaluating microparticle performance. The IVIVCs demonstrate that in vitro release at 37 °C may not accurately represent the in vivo conditions (i.e., subcutaneous space in rodents), and in certain instances lower in vitro release temperatures may more accurately represent the in vivo microenvironment and provide better correlations. Future studies will determine the extent temperature and specifically co-housing, may have on the relative impact of the in vivo performance of injectable polymeric microparticles based upon the significant differences observed in the in vitro release profiles across the range of 35-37 °C., (Copyright © 2021. Published by Elsevier B.V.)

The isolation and spectroscopic data of a hitherto undescribed polyketide ( 1 ) from Hypericum roeperianum Schimp. (Hypericaceae) together with six known compounds ( 2 - 7 ) is herein reported. The structure elucidation is based on extensive 1D- and 2D-NMR, infrared, UV and MS experiments. The structures of the known compounds were confirmed by comparison of their spectroscopic data with those of similar reported compounds in the literature. Some of the isolated compounds had a significant activity against a panel of multidrug-resistant bacterial strains.Supplemental data for this article can be accessed at https://doi.org/10.1080/14786419.2019.1677655.

Background: Despite a longstanding interest in understanding how animals adapt to environments with limited nutrients, we have incomplete knowledge of the genetic basis of metabolic evolution. The Mexican tetra, Astyanax mexicanus, is a species of fish that consists of two morphotypes; eyeless cavefish that have adapted to a low-nutrient cave environment, and ancestral river-dwelling surface fish with abundant access to nutrients. Cavefish have evolved altered blood sugar regulation, starvation tolerance, increased fat accumulation, and superior body condition. To investigate the genetic basis of cavefish metabolic evolution we carried out a quantitative trait loci (QTL) analysis in surface/cave F2 hybrids. We genetically mapped seven metabolism-associated traits in hybrids that were challenged with a nutrient restricted diet., Results: We found that female F2 hybrids are bigger than males and have a longer hindgut, bigger liver, and heavier gonad, even after correcting for fish size. Although there is no difference between male and female blood sugar level, we found that high blood sugar is associated with weight gain in females and lower body weight and fat level in males. We identified a significant QTL associated with 24-h-fasting blood glucose level with the same effect in males and females. Differently, we identified sex-independent and sex-dependent QTL associated with fish length, body condition, liver size, hindgut length, and gonad weight. We found that some of the genes within the metabolism QTL display evidence of non-neutral evolution and are likely to be under selection. Furthermore, we report predicted nonsynonymous changes to the cavefish coding sequence of these genes., Conclusions: Our study reveals previously unappreciated genomic regions associated with blood glucose regulation, body condition, gonad size, and internal organ morphology. In addition, we find an interaction between sex and metabolism-related traits in A. mexicanus. We reveal coding changes in genes that are likely under selection in the low-nutrient cave environment, leading to a better understanding of the genetic basis of metabolic evolution.

Carotenoids are lipid-soluble yellow to orange pigments produced by plants, bacteria, and fungi. They are consumed by animals and metabolized to produce molecules essential for gene regulation, vision, and pigmentation. Cave animals represent an interesting opportunity to understand how carotenoid utilization evolves. Caves are devoid of light, eliminating primary production of energy through photosynthesis and, therefore, limiting carotenoid availability. Moreover, the selective pressures that favor carotenoid-based traits, like pigmentation and vision, are relaxed. Astyanax mexicanus is a species of fish with multiple river-adapted (surface) and cave-adapted populations (i.e., Tinaja, Pachón, Molino). Cavefish exhibit regressive features, such as loss of eyes and melanin pigment, and constructive traits, like increased sensory neuromasts and starvation resistance. Here, we show that, unlike surface fish, Tinaja and Pachón cavefish accumulate carotenoids in the visceral adipose tissue. Carotenoid accumulation is not observed in Molino cavefish, indicating that it is not an obligatory consequence of eye loss. We used quantitative trait loci mapping and RNA sequencing to investigate genetic changes associated with carotenoid accumulation. Our findings suggest that multiple stages of carotenoid processing may be altered in cavefish, including absorption and transport of lipids, cleavage of carotenoids into unpigmented molecules, and differential development of intestinal cell types involved in carotenoid assimilation. Our study establishes A. mexicanus as a model to study the genetic basis of natural variation in carotenoid accumulation and how it impacts physiology., (© 2020 Wiley Periodicals LLC.)

The global cancer burden remains a serious concern with the alarming incidence of one in eight men and one in eleven women dying in developing countries. This situation is aggravated by the multidrug resistance (MDR) of cancer cells that hampers chemotherapy. In this study, the cytotoxicity of the methanol extract (HRB), fractions (HRBa, HRBb, and HRBa1-5), and compounds from the bark of Hypericum roeperianum (HRB) was evaluated towards a panel of 9 cancer cell lines. The mode of action of the HRB and trichadonic acid ( 1 ) was also studied. Column chromatography was applied to isolate the constituents of HRB. The cytotoxicity of botanicals and phytochemicals was evaluated by the resazurin reduction assay (RRA). Caspase-Glo assay was used to evaluate the activity of caspases, and reactive oxygen species (ROS) (H 2 DCFH-DA) were assessed by flow cytometry. Phytochemicals isolated from HRB were trichadonic acid ( 1 ), fridelan-3-one ( 2 ), 2-hydroxy-5-methoxyxanthone ( 3 ), norathyriol ( 4 ), 1,3,5,6-tetrahydroxyxanthone ( 5 ), betulinic acid ( 6 ), 3'-hydroxymethyl-2'-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5',6':5,6-(6,8-dihydroxyxanthone)-1',4'-dioxane ( 7 ), and 3'-hydroxymethyl-2'-(4″-hydroxy-3″,5″-dimethoxyphenyl)-5',6':5,6-(xanthone)-1',4'-dioxane ( 8 ). Botanicals HRB, HRBa, HRBa2-4, HRBb, and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines. The recorded IC 50 values ranged from 11.43  µ g/mL (against the P-glycoprotein (gp)-overexpressing CEM/ADR5000 leukemia cells) to 26.75  µ g/mL (against HCT116 (p53 +/+ ) colon adenocarcinoma cells) for the crude extract HRB. Compounds 1 , 5 , and doxorubicin displayed cytotoxic effects towards the 9 tested cancer cell lines with IC 50 values varying from 14.44  µ M (against CCRF-CEM leukemia cells) to 44.20  µ M (against the resistant HCT116 (p53 -/- ) cells) for 1 and from 38.46  µ M (against CEM/ADR5000 cells) to 112.27  µ M (against the resistant HCT116 (p53 -/- ) cells) for 5 . HRB and compound 1 induced apoptosis in CCRF-CEM cells. The apoptotic process was mediated by enhanced ROS production for HRB or via caspases activation and enhanced ROS production for compound 1 . This study demonstrated that Hypericum roeperianum is a potential source of cytotoxic phytochemicals such as trichadonic acid and could be further exploited in cancer chemotherapy., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Michel-Gael F. Guefack et al.)

Background: Recalcitrant cancers appear as a major obstacle to chemotherapy, prompting scientists to intensify the search for novel drugs to tackle the cell lines expressing multi-drug resistant (MDR) phenotypes., Purpose: The purpose of this study was to evaluate the antiproliferative potential of a ferrulic acid derivative, 8,8-bis-(dihydroconiferyl)-diferulate (DHCF2) on a panel of 18 cancer cell lines, including various sensitive and drug-resistant phenotypes, belonging to human and animals. The mode of induction of cell death by this compound was further studied., Methods: The antiproliferative activity, autophagy, ferroptotic and necroptotic cell death were evaluated by the resazurin reduction assay (RRA). CCRF-CEM leukemia cells were used for all mechanistic studies. A caspase-Glo assay was applied to evaluate the activity of caspases. Cell cycle analysis (PI staining), apoptosis (annexin V/PI staining), mitochondrial membrane potential (MMP) (JC-1) and reactive oxygen species (ROS) (H 2 DCFH-DA) were assessed by flow cytometry., Results: DHCF2 demonstrated impressive cytotoxic effects towards the 18 cancer cell lines tested, with IC 50 values all below 6.5 µM. The obtained IC 50 values were in the range of 1.17 µM (towards CCRF-CEM leukemia cells) to 6.34 µM (towards drug-resistant HCT116 p53 -/- human colon adenocarcinoma cells) for DHCF2 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against multidrug-resistant CEM/ADR5000 leukemia cells) for the reference drug, doxorubicin. DHCF2 had IC 50 values lower than those of doxorubicin, against CEM/ADR5000 cells and on some melanoma cell lines, such as MaMel-80a cells, Mel-2a cells, MV3 cells and SKMel-505 cells. DHCF2 induced autophagy as well as apoptosis in CCRF-CEM cells though caspases activation, MMP alteration and increase of ROS production., Conclusion: The studied diferulic acid, DHCF2, is a promising antiproliferative compound. It deserves further indepth investigations with the ultimate aim to develop a novel drug to fight cancer drug resistance., Competing Interests: Declaration of Competing Interest There is no conflict of interest., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

The effectiveness of anticancer chemotherapy is greatly impeded by the resistance of malignant cells to cytotoxic drugs. In this study, the cytotoxicity of the crude extract (DCB) and compounds isolated from the bark of Dichrostachys cinerea, namely, betulinic acid ( 1 ), glyceryl-1-hexacosanoate ( 2 ), 7-hydroxy-2-(4-hydroxyphenyl)-4 H -chromen-4-one ( 3 ), and 6-hydroxy-2-(4-hydroxyphenyl)-4 H -chromen-4-one ( 4 ), was investigated. The study was extended to the assessment of the mode of induction of apoptosis by DCB and compound 1 . The resazurin reduction assay was used for cytotoxicity studies. Assessments of cell cycle distribution, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were performed by flow cytometry. Constituents of DCB were isolated by column chromatography. Triterpenoid 1 and flavone 4 had cytotoxic effects towards the 9 tested cancer cell lines with IC 50 values below 50 μ M. The recorded IC 50 values varied from 7.65 μ M (towards multidrug-resistant CEM-ADR5000 leukemia cells) to 44.17 μ M (against HepG2 hepatocarcinoma cells) for 1 , 18.90 μ M (CCRF-CEM leukemia cells) to 88.86 μ M (against HCT116p53 +/+ colon adenocarcinoma cells) for 4, and 0.02 μ M (against CCRF-CEM cells) to 122.96 μ M (against CEM/ADR5000 cells) for doxorubicin. DCB induced apoptosis in CCRF-CEM cells mostly mediated by MMP alteration and enhanced ROS production; compound 1 induced apoptosis through caspases activation and MMP alteration and increased ROS production. Dichrostachys cinerea is an interesting cytotoxic plant and deserves more studies leading to new antineoplastic agents to fight cancer and mostly leukemia.

Ethnopharmacological Relevance: Fagara tessmannii Engl. is an African medicinal plant used in Cameroonian traditional medicine to treat various types of cancers., Aim of the Study: This work was designed to determine the cytotoxicity of the crude extract (FTB), fractions (FTBa-d) and compounds isolated from the bark of Fagara tessmannii, namely lupeol (1), fagaramide (2), zanthoxyline (3), hesperidin (4), nitidine chloride (5), fagaridine chloride (6), and β-sitosterol-3-O-β- D -glucopyranoside (7). The study was extended to the mode of induction of apoptosis by FTB, compounds 5 and 6., Materials and Methods: The resazurin reduction assay was used to evaluate the cytotoxicity of samples. The cell cycle, apoptosis, mitochondrial membrane potential (MMP), and reactive oxygen species (ROS) were measured by flow cytometry. Column chromatography was used for the purification of FTB. Meanwhile, nuclear magnetic resonance (NMR) spectroscopic analysis was applied for structural elucidation., Results: The crude extract, fractions FTBa, FTBc, FTBd as well as compounds 5 and 6 revealed cytotoxicity towards the 9 tested cancer cell lines. The IC 50 values ranged from 17.34 µg/mL (towards U87MG.ΔEGFR glioblastoma cells) to 40.68 µg/mL (against CCRF-CEM leukemia cells) for FTB, from 16.78 µg/mL (towards U87. MGΔEGFR cells) to 37.42 µg/mL (against CEM/ADR5000 leukemia cells) for FTBa, from 19.47 µg/mL (towards U87. MG glioblastoma cells) to 41.62 µg/mL (against CCRF-CEM cells) for FTBc, from 14.17 µg/mL (against HCT116p53 -/- colon adenocarcinoma cells) to 22.28 µg/mL (towards CEM-ADR5000 cells) for FTBd, from 1.75 µM (against CCRF-CEM cells) to 23.52 µM (against U87. MGΔEGFR cells) for compound 5, from 1.69 µM (against CCRF-CEM cells) to 22.06 µM (against HepG2 hepatocarcinoma cells) for compound 6 and from 0.02 µM (against CCRF-CEM cells) to 122.96 µM (against CEM/ADR5000 cells) for doxorubicin. FTB induced apoptosis in CCRF-CEM cells mediated by enhanced ROS production. Compound 5 induced apoptosis through caspases activation and increase ROS production. Meanwhile, 6 induced apoptosis mediated by caspases activation, MMP alteration and enhanced ROS production., Conclusion: Fagara tessmannii as well as its constituents 5 and 6 revealed considerable cytotoxicity and may be suitable candidates deserving to be further explored to develop new anticancer drugs to combat sensitive and resistant phenotypes., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Quantifying dynamic strain fields from time-resolved volumetric medical imaging and microscopy stacks is a pressing need for radiology and mechanobiology. A critical limitation of all existing techniques is regularization: because these volumetric images are inherently noisy, the current strain mapping techniques must impose either displacement regularization and smoothing that sacrifices spatial resolution, or material property assumptions that presuppose a material model, as in hyperelastic warping. Here, we present, validate, and apply the first three-dimensional (3D) method for estimating mechanical strain directly from raw 3D image stacks without either regularization or assumptions about material behavior. We apply the method to high-frequency ultrasound images of mouse hearts to diagnose myocardial infarction. We also apply the method to present the first ever in vivo quantification of elevated strain fields in the heart wall associated with the insertion of the chordae tendinae. The method shows promise for broad application to dynamic medical imaging modalities, including high-frequency ultrasound, tagged magnetic resonance imaging, and confocal fluorescence microscopy.

Ethnopharmacological Relevance: Harungana madagascariensis Lam. ex Poir. (Hypericaceae) is used in folk medicine to treat a variety of human ailments, mainly antibacterial, antifungal, antiviral and viral infections. In the present study, the methanol extract from the leaves (HML) and bark (HMB) of this plant as well as fractions (HMBa-c), sub-fractions (HMBa1-5) and compounds isolated from HMBa and HMBb namely betulinic acid (1), madagascin (2), ferruginin A (3) and Kaempferol-3-O-β-d-glucopyranoside (4) were tested for their antimicrobial activities against a panel of 28 g-negative bacteria including multidrug resistant (MDR) phenotypes., Materials and Methods: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; column chromatography was used for the fractionation and purification of the bark extract whilst the chemical structures of compounds were determined using spectroscopic techniques., Results: Crude extract HMB together with fraction HMBa and sub-fraction HMBa3 were active on the 28 tested bacterial strains. HML as well as fractions HMBb, HMBc and sub-fractions HMBa1, HMBa2, HMBa4 and HMBa5 were selectively active. MIC values below or equal to 1024µg/mL were recorded with these samples on 92.9% (for HML and HMBa 4), 82.1% (for HMBb), 78.6% (for HMBa2), 50.0% (for HMBa5) and 42.9% (for HMBc) tested bacteria. For crude material, the lowest MIC value below 8µg/mL was obtained with HMB against Escherichia coli ATCC10536 and W3110 strains, and with sub-fraction HMBa3 against Klebsiella pneumoniae K2 strains. MIC values below 10µg/mL were recorded with compound 3 against E. coli ATCC10536, Enterobacter aerogenes ATCC13048 and EA294, Pseudomonas aeruginosa PA01, K. pneumoniae K2 and Kp55 and Enterobacter cloacae BM67., Conclusions: Harungana madagascariensis is a potential source of antimicrobial drugs to fight against MDR bacteria. The anthranol 3 is the main antibacterial constituents of the bark of the plant. HMB and compound 3 deserve further investigations to develop natural drug to combat Gram-negative bacteria and otherwise MDR phenotypes., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Ethnopharmacological Relevance: Fagara tessmannii is a shrub of the African rainforests used to treat bacterial infections, cancers, swellings and inflammation. In the present study, the methanol extract from the leaves (FTL), bark (FTB), and roots (FTR) of this plant as well as fractions (FTR1-5) and compounds isolated from FTR namely β-sitosterol-3-O-β-d-glucopyranoside (1), nitidine chloride (2) and buesgenine (3), were tested for their antimicrobial activities against a panel of Gram-negative bacteria including multidrug resistant (MDR) phenotypes., Materials and Methods: The broth microdilution method was used to determine the minimal inhibitory concentration (MIC) and minimal bactericidal concentration (MBC) of the above samples; Column chromatography was used for the fractionation and purification of the roots extract whilst the chemical structures of compounds were determined using spectroscopic techniques., Results: Results of the MIC determinations indicated that the crude extracts from the roots as well as fraction FTRa4 were active on all the 26 tested bacterial strains. MIC values below 100µg/mL were obtained with roots, leaves and bark extract respectively against 30.8%, 15.4% and 11.5% tested bacteria. The lowest MIC value below of 8µg/mL was obtained with extract from the roots against Escherichia coli MC100 strain. The lowest MIC value of 4µg/mL was also obtained with compound 3 against E. coli AG102 and Klebsiella pneumoniae ATCC11296 CONCLUSIONS: The present study demonstrates that F. tessmannii is a potential source of antimicrobial drugs to fight against MDR bacteria. Benzophenanthrine alkaloids 2 and 3 are the main antibacterial consituents of the roots of the plant., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Treatment of high-grade primary brain tumors is based on experience from multicenter trials. However, the prognosis has changed little in 3 decades. This suggests that there is a fundamental oversight in treatment. This article provides an imaging perspective of how regional responses of primary brain tumors may be examined to guide a flexible treatment plan. Sodium imaging provides a measurement of cell density that can be used to measure regional cell kill. Such a bioscales of regionally and temporally sensitive biologic-based parameters may be helpful to guide tumor treatment. These suggestions are speculative and still being examined, but are presented to challenge the medical community to be receptive to changes in the standard of care when that standard continues to fail.

The effects of prolonged exposure to 2 and 10 microM 6-mercaptopurine (6MP) in the human lymphoblastic T-cell line MOLT-4 were studied with respect to cell-kinetic parameters, phosphoribosyl pyrophosphate (PRPP) and purine ribonucleotide levels, formation of 6MP-nucleotides, especially methyl-thio-IMP (Me-tIMP), DNA and RNA synthesis ([32P] incorporation), and [8-14C]6MP incorporation into newly synthesized DNA and RNA. The results provided new insights into the complex mechanism of action of 6MP in human malignant lymphoblasts. Exposure to 2 microM 6MP resulted in a rapid inhibition of purine de novo synthesis (PDNS) by increased levels of Me-tIMP, resulting in increased PRPP levels and decreased purine ribonucleotides, affecting cell growth and clonal growth, and less cell death. DNA synthesis decreased, associated with an increasing delay of cells in S phase. Incorporation of thioguanine nucleotides into newly synthesized DNA resulted in an increasing arrest of cells in G2 + M phase. RNA synthesis, initially decreased, recovered partially, associated with a recovery of purine ribonucleotides. New formation of 6MP-nucleotides (tIMP) was only detected within the first 24 hr, and 6MP levels in the culture medium were already undetectable after 6 hr of exposure to 2 microM, indicating a high rate of incorporation and complete conversion of 6MP within this period. Incorporation of 6MP-nucleotides into DNA was 5 times as high as incorporation into RNA. Exposure to 10 microM 6MP resulted in early cytotoxicity at 24 hr, associated with a complete inhibition of PDNS by a large pool of Me-tIMP and lower levels of purine ribonucleotides as compared to 2 microM 6MP. A more severe delay of cells in S phase was associated with an inhibition of DNA synthesis to 14% of control within the first 24 hr, and an arrest in G2 + M phase. Further increasing levels of Me-tIMP caused an arrest of cells and late cytotoxicity in S phase at 48 hr, preventing further progression into G2 + M phase. Our data suggest that inhibition of PDNS due to Me-tIMP is a crucial event in the mechanism of 6MP cytotoxicity. It is responsible for decreased RNA synthesis and decreased availability of natural deoxyribonucleotides, causing a delay of DNA synthesis in S phase. This enhances incorporation of 6MP as thioguanine nucleotides into DNA in the S phase and subsequent late cytotoxicity in the G2 phase. However, with high concentrations of 6MP, the large pool of Me-tIMP causes severe reduction of natural deoxyribonucleotides in lymphoblasts with an active PDNS.(ABSTRACT TRUNCATED AT 400 WORDS)

1 A modified technique for the measurement of O-dealkylase (ODA) activity in crude homogenates is reported, and its application to skin is described. 2 Large differences in ODA levels were found between different species, no activity being observed in the skin of primates. 3 Induction of cutaneous ODA in mice was achieved by the subcutaneous injection of phenobarbitone, hexachlorobenzene or 20-methylcholanthrene. 4 Attempts to induce ODA in vitro were unsuccessful.