Search results for: combined inhibition

Authors: Ncoza Dlova, Tivani Mashamba-Thompson

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Garcinia livingstonei (Clusiaceae) extracts, morelloflavone- 7″- sulphate and sargaol were shown to be effective against hyper-pigmentation through inhibition of tyrosinase enzyme, in vitro . The aim of this study is to elucidate the structural mechanism through which morelloflavone- 7″- sulphate and sargaol binds human tyrosinase. Implementing a homology model to construct a tyrosinase model using the crystal structure of a functional unit from Octopus hemocyanin (PDB: 1JS8) as a reference template enabled us to create a human tyrosinase model. Molecular dynamics and binding free energy calculations were optimized to enable molecular dynamics simulation of the copper dependent inhibitors. Results show the importance of the hydrogen bond formation morelloflavone- 7″- sulphate and sargaol between compound and active site residues. Both complexes demonstrated the metallic coordination between compound and arginine residue as well as copper ions within the active site. The comprehensive molecular insight gained from this study should be vital in understanding the binding mechanism morelloflavone- 7″- sulphate and sargaol. Moreover, these results will assist in the design of novel of metal ion dependent enzyme inhibitors as potential anti-hyper-pigmentation disorder therapies.

Keywords: hyper-pigmentation disorders, dyschromia African skin, morelloflavone- 7″- sulphate, sagoal

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Authors: Ivana Yuniarti, Iwan Ridwansyah

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This paper delivers a review of various methodologies for habitat assessment and a proposed methodology to assess an endemic fish species habitat in Lake Maninjau, Indonesia as a part of a Ph.D. project. This application is mainly aimed to assess the trade-off between the economic value of aquaculture and the fisheries. The proposed methodology is a generalized linear model (GLM) combined with GIS to assess presence-absence data or habitat suitability index (HSI) combined with the analytical hierarchy process (AHP). Further, a cost of habitat replacement approach is planned to be used to calculate the habitat value as well as its trade-off with the economic value of aquaculture. The result of the study is expected to be a scientific consideration in local decision making and to provide a reference for other areas in the country.

Keywords: AHP, habitat, GLM, HSI, Maninjau

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Authors: Faraj M. Elkhatri, Hana Ellafi

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: formation damage, porosity loses, pore throat, quartz cement

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Authors: Lixin Tian, Wei Xue

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Many jobs in society go underground, such as mine mining, tunnel construction and subways, which are vital to the development of society. Once accidents occur in these places, the interruption of traditional wired communication is not conducive to the development of rescue work. In order to realize the positioning, early warning and command functions of underground personnel and improve rescue efficiency, it is necessary to develop and design an emergency ground communication system. It is easy to be subjected to narrowband interference when performing conventional underground communication. Spreading communication can be used for this problem. However, general spread spectrum methods such as direct spread communication are inefficient, so it is proposed to use parallel combined spread spectrum (PCSS) communication to improve efficiency. The PCSS communication not only has the anti-interference ability and the good concealment of the traditional spread spectrum system, but also has a relatively high frequency band utilization rate and a strong information transmission capability. So, this technology has been widely used in practice. This paper presents a PCSS communication model-multiple detection parallel combined spread spectrum (MDPCSS) communication system. In this paper, the principle of MDPCSS communication system is described, that is, the sequence at the transmitting end is processed in blocks and cyclically shifted to facilitate multiple detection at the receiving end. The block diagrams of the transmitter and receiver of the MDPCSS communication system are introduced. At the same time, the calculation formula of the system bit error rate (BER) is introduced, and the simulation and analysis of the BER of the system are completed. By comparing with the common parallel PCSS communication, we can draw a conclusion that it is indeed possible to reduce the BER and improve the system performance. Furthermore, the influence of different pseudo-code lengths selected on the system BER is simulated and analyzed, and the conclusion is that the larger the pseudo-code length is, the smaller the system error rate is.

Keywords: cyclic shift, multiple detection, parallel combined spread spectrum, PN code

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Authors: M. R. Gad El- Kareem, A. M. K. Abdel Aal, A. Y. Mohamed

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During 2011 and 2012 seasons, Zaghloul date palms received four sprays of silicon (Si) at 0.05 to 0.1% and selenium (Se) at 0.01 to 0.02%. Growths, nutritional status, yield as well as physical and chemical characteristics of the fruits in response to application of silicon and selenium were investigated. Single and combined applications of silicon at 0.05 to 0.1% and selenium at 0.01 to 0.02% was very effective in enhancing the leaf area, total chlorophylls, percentages of N, P, and K in the leaves, yield, bunch weight as well as physical and chemical characteristics of the fruits in relative to the check treatment. Silicon was superior to selenium in this respect. Combined application was favourable than using each alone in this connection. Treating Zaghloul date palms four times with a mixture of silicon at 0.05% + selenium at 0.01% resulted in an economical yield and producing better fruit quality.

Keywords: date palms, Zaghloul, silicon, selenium, leaf area

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Authors: Abazar Ghorbani, W. M. Wishwajith W. Kandegama, Seyed Mehdi Razavi, Moxian Chen

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The roles of hydrogen sulfide (H₂S) and melatonin (MT) as gasotransmitters in plants are widely recognised. Nevertheless, the precise nature of their involvement in defensive reactions remains uncertain. This study investigates the impact of the ML-H2S interaction on tomato plants exposed to vanadium (V) toxicity, focusing on synthesising secondary metabolites and V metal sequestration. The treatments applied in this study included a control (T1), V stress (T2), MT+V (T3), MT+H2S+V (T4), MT+hypotaurine (HT)+V (T5), and MT+H2S+HT+V (T6). These treatments were administered: MT (150 µM) as a foliar spray pre-treatment (3X), HT treatment (0.1 mM, an H2S scavenger) as root immersion for 12 hours as pre-treatments, and H2S (NaHS, 0.2 mM) and V (40 mg/L) treatments added to the Hoagland solution for 2 weeks. Results demonstrate that ML and H2S+ML treatments alleviate V toxicity by promoting the transcription of key genes (ANS, F3H, CHS, DFR, PAL, and CHI) involved in phenolic and anthocyanin biosynthesis. Moreover, they decreased V uptake and accumulation and enhanced the transcription of genes involved in glutathione and phytochelatin synthesis (GSH1, PCS, and ABC1), leading to V sequestration in roots and protection against V-induced damage. Additionally, ML and H2S+ML treatments optimize chlorophyll metabolism, and increase internal H2S levels, thereby promoting tomato growth under V stress. The combined treatment of ML+H2S shows superior effects compared to ML alone, suggesting synergistic/interactive effects between these two substances. Furthermore, inhibition of the beneficial impact of ML+H2S and ML treatments by HT, an H2S scavenger, underscores the significant involvement of H₂S in the signaling pathway activated by ML during V toxicity. Overall, these findings suggest that ML requires the presence of endogenous H₂S to mitigate V-induced adverse effects on tomato seedlings.

Keywords: vanadium toxicity, secondary metabolites, vanadium sequestration, h2s-melatonin crosstalk

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Authors: Adria Rae Abigail R. Eda, Arvin C. Diesmos, Vance T. Vredenburg, Merab A. Chan

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Mitigating strategies using symbiotic cutaneous bacteria is one of the major concerns in the conservation of amphibian population. Batrachochytrium dendrobatidis is the causative agent of chytridiomycosis associated with mass mortality and amphibian extinctions worldwide. In the Philippines, there is a lack of study on the cutaneous bacteria of Philippine amphibians that may have beneficial effects to ward off the deadly fungal infection. In this study, cutaneous bacteria from frogs were isolated and examined for anti-B. dendrobatidis activity. Eight species of frogs were collected at Mt. Palay-palay Mataas na Gulod National Park in Cavite, a site positive for the presence of B. dendrobatidis. Bacteria were isolated from the skin of frogs by swabbing the surfaces of the body and inoculated in Reasoner´s 2A (R2A) agar. Isolated bacteria were tested for potential inhibitory properties against B. dendrobatidis through zoospore inhibition assay. Results showed that frog cutaneous bacteria significantly inhibited the growth of B. dendrobatidis in vitro. By means of 16S rRNA gene primers, the anti-B. dendrobatidis bacteria were identified to be Enterobacter sp., Alcaligenes faecalis and Pseudomonas sp. Cutaneous bacteria namely Enterobacter sp. (isolates PLd33 and PCv4) and Pseudomonas (isolate PLd31) remarkably cleared the growth of B. dendrobatidis zoospore in 1% tryptone agar. Therefore, frog cutaneous bacteria inhibited B. dendrobatidis in vitro and could possibly contribute to the immunity and defense of frogs against the lethal chytridiomycosis.

Keywords: Batrachochytrium dendrobatidis, cutaneous bacteria, frogs, zoospore inhibition assay

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Authors: Asma Ben Hmidene, Mizuho Hanaki, Kazuma Murakami, Kazuhiro Irie, Hiroko Isoda, Hideyuki Shigemori

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Type 2 diabetes mellitus (T2DM) and Alzheimer’s disease (AD) are characterized as a peripheral metabolic disorder and a degenerative disease of the central nervous system, respectively. It is now widely recognized that T2DM and AD share many pathophysiological features including glucose metabolism, increased oxidative stress and amyloid aggregation. Amyloid beta (Aβ) is the components of the amyloid deposits in the AD brain and while the component of the amyloidogenic peptide deposit in the pancreatic islets of Langerhans is identified as human islet amyloid polypeptide (hIAPP). These two proteins are originated from the amyloid precursor protein and have a high sequence similarity. Although the amino acid sequences of amyloidogenic proteins are diverse, they all adopt a similar structure in aggregates called cross-beta-spine. Add at that, extensive studies in the past years have found that like Aβ1-42, IAPP forms early intermediate assemblies as spherical oligomers, implicating that these oligomers possess a common folding pattern or conformation. These similarities can be used in the search for effective pharmacotherapy for DM, since potent therapeutic agents such as antioxidants with a catechol moiety, proved to inhibit Aβ aggregation, may play a key role in the inhibit the aggregation of hIAPP treatment of patients with DM. Tamarix gallica is one of the halophyte species having a powerful antioxidant system. Although it was traditionally used for the treatment of various liver metabolic disorders, there is no report about the use of this plant for the treatment or prevention of T2DM and AD. Therefore, the aim of this work is to investigate their protective effect towards T2DM and AD by isolation and identification of α-glucosidase inhibitors, with antioxidant potential, that play an important role in the glucose metabolism in diabetic patient, as well as, the polymerization of hIAPP and Aβ aggregation inhibitors. Structure-activity relationship study was conducted for both assays. And as for α-glucosidase inhibitors, their mechanism of action and their synergistic potential when applied with a very low concentration of acarbose were also suggesting that they can be used not only as α-glucosidase inhibitors but also be combined with established α-glucosidase inhibitors to reduce their adverse effect. The antioxidant potential of the purified substances was evaluated by DPPH and SOD assays. Th-T assay using 42-mer amyloid β-protein (Aβ42) for AD and hIAPP which is a 37-residue peptide secreted by the pancreatic β –cells for T2DM and Transmission electronic microscopy (TEM) were conducted to evaluate the amyloid aggragation of the actives substances. For α-glucosidase, p-NPG and glucose oxidase assays were performed for determining the inhibition potential and structure-activity relationship study. The Enzyme kinetic protocol was used to study the mechanism of action. From this research, it was concluded that polyphenols playing a role in the glucose metabolism and oxidative stress can also inhibit the amyloid aggregation, and that substances with a catechol and glucuronide moieties inhibiting amyloid-β aggregation, might be used to inhibit the aggregation of hIAPP.

Keywords: α-glucosidase inhibitors, amyloid aggregation inhibition, mechanism of action, polyphenols, structure activity relationship, synergistic potential, tamarix gallica

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Authors: Yonghwa Lee, Yoon Suk Kim, Yongsub Yi

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This study was to confirm the effects of anti-melanogenesis and anti-inflammatory effects from Opuntia humifusa fruit and stem extracts. A potent anti-oxidant activity was shown from the leaf extract at IC50 value of 38.33±1.07 μg/mL and fruit extract at IC50 value of 40.23±2.21 μg/mL by 1,1-diphenyl-2-picrylhydrazyl (DPPH) assay. Also, phenolic contents were confirmed total phenolic assay by high performance liquid chromatography (HPLC). Fraction of taxifolin from leaf extract was identified using HPLC and gas chromatography/mass spectrometry. The extracts of Opuntia humifusa fruit and stem were confirmed about toxicity effect in B16 F1 by cell viability. Melanin contents were decreased. Opuntia humifusa fruit and stem extracts had a positive effect of melanin synthesis inhibition for skin whitening. In investigating the anti-inflammatory activities of Opuntia humifusa, the results of cell viability indicated that taxifolin did not show cytotoxicity on RAW264.7 cells at 500 μM of concentration. The results show that taxifolin inhibited lipopolysaccharide (LPS)-induced production of Nitrite oxide (NO). In addition, taxifolin indicated the inhibition of lipopolysaccharide (LPS)-induced tumor necrosis factor (TNF) -α and interleukin (IL) -6 productions by cytokine assay and cyclooxygenase (COX)-2 expression by western blot analysis, meaning that taxifolin had a significant anti-inflammatory effect. Our results suggested that taxifolin from Opuntia humifusa has anti-melanogenesis and anti-inflammatory activities.

Keywords: anti-melanogenesis, anti-inflammatory, Opuntia humifusa, taxifolin

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Authors: Abdulaziz Bashir Kutawa, Khairulmazmi Ahmad, Mohd Zobir Hussein, Asgar Ali, Mohd Aswad Abdul Wahab, Amara Rafi, Mahesh Tiran Gunasena, Muhammad Ziaur Rahman, Md. Imam Hossain, Syazwan Afif Mohd Zobir

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Rice is a cereal crop and belongs to the family Poaceae, it was domesticated in southern China and North-Eastern India around 8000 years ago, and it’s the staple nourishment for over half of the total world’s population. Rice production worldwide is affected by different abiotic and biotic stresses. Diseases are important challenges for the production of rice, among all the diseases in rice plants, the most severe and common disease is the rice blast. Worldwide, it is one of the most damaging diseases affecting rice cultivation, the disease is caused by the non-obligate filamentous ascomycete fungus called Magnaporthe grisae or Pyricularia oryzae Cav. Nanotechnology is a new idea to improve agriculture by combating the diseases of plants, as nanoparticles were found to possess an inhibitory effect on different species of fungi. This work aimed to develop and determine the efficacy of agronanofungicides, and commercial fungicides (in-vitro and in-vivo). The agronanofungicides were developed using ionic gelation methods. In-vitro antifungal activity of the synthesized agronanofungicides was evaluated against P. oryzae using the poisoned medium technique. The potato dextrose agar (PDA) was amended in several concentrations; 0.001, 0.005, 0.01, 0.025, 0.05, 0.1, 0.15, 0.20, 0.25, 0.30, and 0.35 ppm for the agronanofungicides. Medium with the only solvent served as a control. Mycelial growth was recorded every day, and the percentage inhibition of radial growth (PIRG) was also calculated. Based on the results of the zone of inhibition, the chitosan-hexaconazole agronanofungicide (2g/mL) was the most effective fungicide to inhibit the growth of the fungus with 100% inhibition at 0.2, 0.25, 0.30, and 0.35 ppm, respectively. The least were found to be propiconazole and basamid fungicides with 100% inhibition only at 100 ppm. In terms of the glasshouse results, the chitosan-hexaconazole-dazomet agronanofungicide (CHDEN) treatment (2.5g/L) was found to be the most effective fungicide to reduce the intensity of the disease with a disease severity index (DSI) of 19.80%, protection index (PI) of 82.26%, lesion length of 1.63cm, disease reduction (DR) of 80.20%, and AUDPC (390.60 Unit2). The least effective fungicide was found to be ANV with a disease severity index (45.60%), protection index (45.24%), lesion length (3.83 cm), disease reduction (54.40%), and AUDPC (1205.75 Unit2). The negative control did not show any symptoms during the glasshouse assay, while the untreated control treatment exhibited severe symptoms of the disease with a DSI value of 64.38%, lesion length of 5.20 cm, and AUDPC value of 2201.85 Unit2, respectively. The treatments of agronanofungicides have enhanced the yield significantly with CHDEN having 239.00 while the healthy control had 113.67 for the number of grains per panicle. The use of CHEN and CHDEN will help immensely in reducing the severity of rice blast in the fields, and this will increase the yield and profit of the farmers that produced rice.

Keywords: chitosan, dazomet, disease severity, efficacy, and blast disease

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Authors: Elena Corina Popescu, Magda Gabriela Bratu

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Increasing interest in keeping bioactive compounds (anthocyanins, vitamin C) and dried fruit quality has motivated the researchers to investigate new combined drying technologies. The aim of this study was to evaluate the effects of convective dryness combined with osmotic dehydration, blanching, microwave treatment and ultrasonic treatment on the quality of dried plums. Osmotic dehydration was achieved by maintaining plums for 1 h in sucrose solution (300Brix). For microwave treatment, the plums were kept at 400 W for 80 sec. For ultrasonic treatment, plums were immersed in distilled water and sonicated for 30 minutes at 40 kHz and 200 W. The blanching consists of immersing plums in hot water at 90°C for 20 seconds and cooling them rapidly. Conventional drying was carried out at 70°C for 630 minutes. Drying curves, drying rate, anthocyanin and vitamin C stability, acidity variation (expressed as malic acid), reducing sugar content, and rehydration capacity of dried plums were analyzed. Blanching led to the largest amount of evaporated water. Blanched plums have had 13.36% less water than sonicated ones. The lowest anthocyanal loss of 34.5% was obtained in osmotically dehydrated plums, and 2.93% vitamin C is found in the plums sonicated. There were no significant differences in regards acidity and reducing sugar. The plums blanched before drying have had a high capacity of rehydration.

Keywords: anthocyanin, dried plums, pretreatments, vitamin C

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Authors: Mosima M. Mabitsela

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Groundnut is preferably grown on light textured soils. Most of these light textured soils tend to be highly weathered and characterized by high soil acidity and low nutrient status. One major soil factor associated with infertility of acidic soils that can negatively depress groundnut yield is aluminium (Al) toxicity. In plants Al toxicity damages root cells, leading to inhibition of root growth as a result of the suppression of cell division, cell elongation and cell expansion in the apical meristem cells of the root. The end result is that roots become stunted and brittle, root hair development is poor, and the root apices become swollen. This study was conducted to determine the effects of aluminium (Al) toxicity on a range of groundnut varieties. Fifteen cultivars were tested in incremental aluminum (Al) supply in an ebb and flow solution culture laid out in a randomized complete block design. There were six aluminium (Al) treatments viz. 0 µM, 1 µM, 5.7 µM, 14.14 µM, 53.18 µM, and 200 µM. At 1 µM there was no inhibitory effect on the growth of groundnut. The inhibition of groundnut growth was noticeable from 5.7 µM to 200 µM, where the severe effect of aluminium (Al) stress was observed at 200 µM. The cultivars varied in their response to aluminium (Al) supply in solution culture. Groundnuts are one of the most important food crops in the world, and its supply is on a decline due to the light-textured soils that they thrive under as these soils are acidic and can easily solubilize aluminium (Al) to its toxic form. Consequently, there is a need to develop groundnut cultivars with high tolerance to soil acidity.

Keywords: aluminium toxicity, cultivars, reduction, root growth

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Authors: Zhongfei Cai, Hui He, Changsheng Li

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This paper studied in the automatic repeat request (ARQ) transmission technique in Mars detection telecommunications system. An ARQ method applied to proximity-1 space link protocol was proposed by this paper. In order to ensure the efficiency of data reliable transmission, this ARQ method combined these different ARQ maneuvers characteristics. Considering the Mars detection communication environments, this paper analyzed the characteristics of the saturation throughput rate, packet dropping probability, average delay and energy efficiency with different ARQ algorithms. Combined thus results with the theories of ARQ transmission technique, an ARQ transmission project in Mars detection telecommunications system was established. The simulation results showed that this algorithm had excellent saturation throughput rate and energy efficiency with low complexity.

Keywords: ARQ, mars, CCSDS, proximity-1, deepspace

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Authors: Cheng-Chih Tsai, Yu-Hsuan Liu, Cheng-Ying Ho, Chun-Chin Huang

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The aim of this study evaluated the in vitro and in vivo antimicrobial activity of selected lactic acid bacteria (LAB) against Uropathogenic Escherichia coli (UPEC) for prevention and amelioration of UTIs. We screened LAB strains with antimicrobial effects on UPEC using a well-diffusion assay, bacterial adherence to the uroepithelium cell line SV-HUC-1 (BCRC 60358), and a coculture inhibition assay. The results showed that the 7 LAB strains (Lactobacillus paracasei, L. salivarius, two Pediococcus pentosaceus strains, two L. plantarum strains, and L. crispatus) and the fermented probiotic products produced by these multi-LAB strains exhibited potent zones of inhibition against UPEC. Moreover, the LAB strains and probiotic products adhered strongly to the uroepithelium SV-HUC-1 cell line. The growth of UPEC strains was also markedly inhibited after co-culture with the LAB strains and probiotic products in human urine. In addition, the enhanced levels of IL-6, IL-8 and lactic acid dehydrogenase were significantly decreased by treatments with the LAB strains and probiotic products in UPEC-induced SV-HUC-1 cells. Furthermore, oral administration of probiotic products reduced the number of viable UPEC in the urine of UPEC-challenged BALB/c mice. Taken together, this study demonstrates that probiotic supplementation may be useful as an adjuvant therapy for the treatment of bacterial-induced urinary tract infections.

Keywords: lactic acid bacterium, SV-HUC-1 uroepithelium, urinary tract infection, uropathogenic Escherichia coli, BALB/c mice

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Authors: Naresh Radaliyagoda, Nigel M. Jennett, Rong Lan, David Parfitt

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A series of length scale engineered multilayer material with temperature robust mechanical properties has been suggested. A range of polycrystalline copper sub-layers with the thickness varying from 1 to 25μm and buried in between two nickel layers was produced using electrodeposition dual bath technique. The structure of the multilayers was characterized using Electron Backscatter Diffraction and Scanning Electron Microscope. The interface effect on the hardness and elastic modulus was tested using Nano-indentation. Results of the grain size and layer thickness measurements, and indentation hardness have been compared. It is found that there is a combined length scale effect that improves mechanical properties in Ni/Cu multilayer structures.

Keywords: nano-indentation, size effect, multilayers, electrodeposition

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Authors: Chi H. Lin, Chi C. Lin, Chih L. Hsieh

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Motor Imagery (MI) alone or combined with action observation (AO) has been shown to enhance motor performance and skill learning. The most effective way to combine these techniques has received limited scientific scrutiny. In the present study, we examined the effects of simultaneous (i.e., observing an action whilst imagining carrying out the action concurrently), alternate (i.e., observing an action and then doing imagery related to that action consecutively) and synthesis (alternately perform action observation and imagery action and then perform observation and imagery action simultaneously) AOMI combinations on improving golf putting performance and learning. Participants, 45 university students who had no formal experience of using imagery for the study, were randomly allocated to one of four training groups: simultaneous action observation and motor imagery (S-AOMI), alternate action observation and motor imagery (A-AOMI), synthesis action observation and motor imagery (A-S-AOMI), and a control group. And it was applied 'Different Experimental Groups with Pre and Post Measured' designs. Participants underwent eighteen times of different interventions, which were happened three times a week and lasting for six weeks. We analyzed the information we received based on two-factor (group × times) mixed between and within analysis of variance to discuss the real effects on participants' golf putting performance and learning about different intervention methods of different types of combined action observation and motor imagery. After the intervention, we then used imagery questionnaire and journey to understand the condition and suggestion about different motor imagery and action observation intervention from the participants. The results revealed that the three experimental groups both are effective in putting performance and learning but not for the control group, and the A-S-AOMI group is significantly better effect than S-AOMI group on golf putting performance and learning. The results confirmed the effect of motor imagery combined with action observation on the performance and learning of golf putting. In particular, in the groups of synthesis, motor imagery, or action observation were alternately performed first and then performed motor imagery, and action observation simultaneously would have the best effectiveness.

Keywords: motor skill learning, motor imagery, action observation, simulation

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Authors: Chun-Ying Lee, Kun-Hsien Lee, Bor-Wei Wang

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The process of post-supercritical CO₂ electroplating uses the electrolyte solution after being mixed with supercritical CO₂ and released to atmospheric pressure. It utilizes the microbubbles that form when oversaturated CO₂ in the electrolyte returns to gaseous state, which gives the similar effect of pulsed electroplating. Under atmospheric pressure, the CO₂ bubbles gradually diffuse. Therefore, the introduction of ultrasound and/or other agitation can potentially excite the CO₂ microbubbles to achieve an electroplated surface of even higher quality. In this study, during the electroplating process, three different modes of agitation: magnetic stirrer agitation, ultrasonic agitation and a combined mode (magnetic + ultrasonic) were applied, respectively, in order to obtain an optimal surface morphology and mechanical properties for the electroplated Ni coating. It is found that the combined agitation mode at a current density of 40 A/dm² achieved the smallest grain size, lower surface roughness, and produced an electroplated Ni layer that achieved hardness of 320 HV, much higher when compared with conventional method, which were usually in the range of 160 to 300 HV. However, at the same time, the electroplating with combined agitation developed a higher internal stress of 320 MPa due to the lower current efficiency of the process and finer grain in the coating. Moreover, a new control methodology for tailoring the coating’s mechanical property through its thickness was demonstrated by the timely introduction of ultrasonic agitation during the electroplating process with post supercritical CO₂ mixed electrolyte.

Keywords: nickel electroplating, micro-bubbles, supercritical carbon dioxide, ultrasonic agitation

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Authors: Pello Alfonso-Muniozguren, Madeleine Bussemaker, Ralph Chadeesingh, Caryn Jones, David Oakley, Judy Lee, Devendra Saroj

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Current industrialized livestock agriculture is growing every year leading to an increase in the generation of wastewater that varies considerably in terms of organic content and microbial population. Therefore, suitable wastewater treatment methods are required to ensure the wastewater quality meet regulations before discharge. In the present study, a combined lab scale activated sludge-filtration-ozonation system was used to treat a pre-treated abattoir wastewater. A hydraulic retention time of 24 hours and a solid retention time of 13 days were used for the activated sludge process, followed by a filtration step (4-7 µm) and using ozone as tertiary treatment. An average reduction of 93% and 98% was achieved for Chemical Oxygen Demand (COD) and Biological Oxygen Demand (BOD), respectively, obtaining final values of 128 mg/L COD and 12 mg/L BOD. For the Total Suspended Solids (TSS), the average reduction increased to 99% in the same system, reducing the final value down to 3 mg/L. Additionally, 98% reduction in Phosphorus (P) and a complete inactivation of Total Coliforms (TC) was obtained after 17 min ozonation time. For Total Viable Counts (TVC), a drastic reduction was observed with 30 min ozonation time (6 log inactivation) at an ozone dose of 71 mg O3/L. Overall, the combined process was sufficient to meet discharge requirements without further treatment for the measured parameters (COD, BOD, TSS, P, TC, and TVC).

Keywords: abattoir waste water, activated sludge, ozone, waste water treatment

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Authors: Alexey Yu. Martynov, Sulejman Bayramov

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Introduction: The myocardial bridging is the most common anomaly of the coronary arteries (CA). Depending on the examination method, the frequency of detected myocardial bridges (MB) varies in a rather wide range. The typical clinical manifestations of MB are angina pectoris, arrhythmias, sudden cardiac death. Objective: To study the incidence of MB in patients hospitalized with coronary artery disease (CAD). To assess clinical manifestations of MB in patients admitted with CAD. Materials and methods: A retrospective analysis of 19159 case histories of patients admitted at clinical city hospital in Moscow from 01.01.2018 to 31.12 2019 with CAD was performed. 9384 patients’ coronary angiographies (CAG) were examined for MB. The localization of MB, the degree of coronary contraction by MB, the number of MB, isolated MB and combined with CAD were assessed. The clinical manifestations of MB were determined. Results: MB was detected in 52 patients all with one myocardial bridge. 20 patients with MB have intact CA, and 32 patients have MB combined with CAD. Among 20 patients with intact CA: I degree of MB contraction (up to 50%) was detected in 9 patients. Clinical manifestations in five cases were angina pectoris, in 3 myocardial infarction (MI) - 1 patients with ST segment elevation MI (STEMI), 2 without ST segment elevation MI (NSTEMI), 1 post-infarction cardiosclerosis (PICS). Stable angina II FC in 3, III FC in 1, vasospastic angina (VSA) in 1 patient. II degree of MB contraction (up to 50-70%) was determined in 9 patients: in seven cases angina pectoris was detected, 1 NSTEMI, 1 PICS. Stable angina II FC in 3, III FC in 1, VSA in 3 patients. III degree of MB contraction (> 70%) detected in 2 patients. II FC stable angina in one case, PICS in another. Among 32 patients having MB combined with CAD I degree of MB contraction was observed in 20 patients. Clinical manifestations in 12 cases were angina pectoris in 8 II FC and in 4 III FC, 7 MI 6 with STEMI and 1 NSTEMI, 1 PICS. II degree of MB contraction was detected in 7 patients, 4 of them had angina pectoris, 3 MI 2 with STEMI and 1 NSTEMI. Stable angina II FC in 3, VSA in 1 patients. III degree of MB contraction was diagnosed in five patients. In two cases, II FC and III FC stable angina were observed, 2 MI with STEMI and NSTEMI, 1 PICS. Conclusions: MB incidence is one in 368 patients with CAD. The most common involvement (68%) is MB combined with CA atherosclerotic lesions. MB with intact CA are detected in one-third (32%) of patients. The first-degree MB contraction is most frequent condition. MI is more often detected in intact CA with first degree MB than in the second degree. The degree of MB contraction was not correlated with the severity of the clinical manifestations.

Keywords: clinical manifestations, coronary angiography, coronary artery disease, myocardial bridging, myocardial infarction, stable angina

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Authors: Kang-Hyun Leem, Myung-Gyou Kim, Hye Kyung Kim

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The prickly pear cactus (Opuntia ficus-indica) has a global distribution and have been used for medicinal benefits such as artherosclerosis, diabetes, gastritis, and hyperglycemia. However, very little information is currently available for their mechanism. The prikly pear variety Opuntia ficus-indica var. Saboten (OFS) is widely cultivated in Cheju Island, southwestern region of Korea, and used as a functional food. Present study investigated the effects of OFS on pancreatic β-cell function using pancreatic islet β cells (HIT cell). Alpha-glucosidase inhibition, glucose uptake, insulin secretion, insulin sensitivity, and pancreatic β cell proliferation were determined. The inhibitory effect of ethanol extract of OFS stem on α-glucosidase enzyme was measured in a cell free system. Glucose uptake was determined using fluorescent glucose analogue, 2-NBDG. Insulin secretion was measured by ELISA assay. Cell proliferation was measured by MTT assay. Ethanol extracts of OFS dose-dependently inhibited α-glucosidase activity as well as glucose uptake. Insulinotrophic effect of OFS extract was observed at high glucose media in pancreatic β-islet cells. Furthermore, pancreatic β cell regeneration was also observed.These results suggest that OFS mediates the antidiabetic activity mainly via α-glucosidase inhibition, glucose uptake, and improved insulin sensitivity.

Keywords: prickly pear cactus, Opuntia ficus-indica var. Saboten, pancreatic islet HIT cells, α-glucosidase, glucose uptake, insulinotrophic

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Authors: Zhenxiang Zhou

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The triose phosphate utilisation (TPU) limitation to leaf photosynthesis is a biochemical process concerning the sub-foliar carbon sink-source (im)balance, in which photorespiration-associated amino acids exports provide an additional outlet for carbon and increases leaf photosynthetic rate. However, whether this process is regulated by whole-plant sink-source relations and nitrogen budgets remains unclear. We address this question by model analyses of gas-exchange data measured on leaves at three growth stages of rice plants grown at two-nitrogen levels, where three means (leaf-colour modification, adaxial vs abaxial measurements, and panicle pruning) were explored to alter source-sink ratios. Higher specific leaf nitrogen (SLN) resulted in higher rates of TPU and also led to the TPU limitation occurring at a lower intercellular CO2 concentration. Photorespiratory nitrogen assimilation was greater in higher-nitrogen leaves but became smaller in cases associated with yellower-leaf modification, abaxial measurement, or panicle pruning. The feedback inhibition of panicle pruning on rates of TPU was not always observed because panicle pruning blocked nitrogen remobilisation from leaves to grains, and the increased SLN masked the feedback inhibition. The (sub)foliar TPU limitation can be modulated by whole-plant source-sink ratios and nitrogen budgets during rice grain filling, suggesting a close link between sub-foliar and whole-plant sink limitations.

Keywords: triose phosphate utilization, sink limitation, panicle pruning, oryza sativa

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Authors: Gholam Hossein Javanmard, Roghayeh Mohammadi Garegozlo

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The present study was a randomized three-group double-blind clinical trial with repeated measures designs which aimed to determine the pure effect and combined effect of mindfulness based-relaxation (MBR) technique and Transcranial Electrical Simulation (tCES) on psychological distress decreasing of patients with type-2 diabetes. The sample of the study consisted of 30 patients with type-2 diabetes who were selected from the Diabetes Association of Bonab city in Iran. The participants were matched and then randomly assigned to the three groups of 10 subjects (MBR, CES, MBR+CES). The subjects received interventions related to their group in 10 individual sessions. Pre-test, post-test, and one-month follow-up were conducted using DASS-42. Analysis of variance with repeated measures showed a significant change in psychological distress. Multivariate covariance analysis and the paired interpersonal comparative test of Ben Foruni indicated that both interventions of MBR and CES have a similar effect on psychological distress decreasing in the post-test and follow-up phase. But, the combined therapy of MBR+CES was more efficient, and it had a more stable effect. However, all three interventions, especially combined intervention of MBR+CES, as efficient and stable treatment, are suggested for improving the psychological status of diabetic patients.

Keywords: mindfulness based-relaxation, transcranial electrical simulation, type 2 diabetes, psychological distress

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Authors: Hesham Hamdy Abdulmohsen, Ahmed Shawky Abdel Aziz, Mona Fawzy Aldaghma

Abstract:

Helical piles have gained significant attention as efficient alternatives for deep foundations due to their rapid installation process and dual functionality in compression and tension. They experience various combinations of axial and lateral loads. While extensive research has explored helical pile behavior under individual axial or lateral loads, the effects of combined axial compression and lateral loads still need further study. This paper compares experimental and numerical (PLAXIS-3D) results for vertical helical-pile groups under combined loads. The study aims to clarify the impact of key factors, including helix location and lateral load direction, on the lateral capacity of helical-pile groups and, consequently, their overall efficiency. The study concludes that the lateral capacity of the helical-pile group significantly depends on the helix location within the pile shaft length. Optimal lateral performance occurs when helices are positioned at a depth ratio of H/L = 0.4. Furthermore, rectangular plan distribution groups exhibit greater lateral capacity when subjected to lateral loads aligned with their long axis. The presence of vertical compression loading enhances the lateral capacity of the group, with the specific enhancement depending on the value of the vertical compression load, lateral load direction, and helix location.

Keywords: experimental, numerical model, lateral loading, group efficiency, helical piles

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Authors: J. Herrero, D. Puigserver, I. Nijenhuis, K. Kuntze, J. M. Carmona

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In the transition zone between aquifers and basal aquitards, the perchloroethene (PCE)-pools are more recalcitrant than those elsewhere in the aquifer. Although biodegradation of chloroethenes occur in this zone, it is a slow process and a remediation strategy is needed. The aim of this study is to demonstrate that combined strategy of biostimulation and in situ chemical reduction (ISCR) is more efficient than the two separated strategies. Four different microcosm experiments with sediment and groundwater of a selected field site where an aged pool exists at the bottom of a transition zone were designed under i) natural conditions, ii) biostimulation with lactic acid, iii) ISCR with zero-value iron (ZVI) and under iv) a combined strategy with lactic acid and ZVI. Biotic and abiotic dehalogenation, terminal electron acceptor processes and evolution of microbial communities were determined for each experiment. The main results were: i) reductive dehalogenation of PCE-pools occurs under sulfate-reducing conditions; ii) biostimulation with lactic acid supports more pronounced reductive dehalogenation of PCE and trichloroethene (TCE), but results in an accumulation of 1,2-cis-dichloroethene (cDCE); iii) ISCR with ZVI produces a sustained dehalogenation of PCE and its metabolites iv) combined strategy of biostimulation and ISCR results in a fast dehalogenation of PCE and TCE and a sustained dehalogenation of cisDCE. These findings suggest that biostimulation and ISCR with ZVI are the most suitable strategies for a complete reductive dehalogenation of PCE-pools in the transition zone and further to enable the dissolution of dense non-aqueous phase liquids.

Keywords: aged PCE-pool, anaerobic microcosm experiment, biostimulation, in situ chemical reduction, natural attenuation

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Authors: Fabiola Trejo Perez, Rolando Diaz Loving

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Sexual pleasure consists of the positively valued feelings induced by sexual stimuli, but it is also weighed down by pop-psychological baggage, and subjected to cross-cultural and cross-historical variation. Social and individual interpretations of what can or can’t be considered as pleasurable are intertwined with culture’s predominant values, norms and beliefs. For each culture, sexual norms work as a guide to be followed in order to model socially accepted behaviors. Therefore, cultural messages regarding sexuality are usually directed to restrict men and women from enjoyment, sexual satisfaction and specifically orgasm. Given that sexual pleasure hasn’t been recognized as an accepted topic of open discussion, particularly for women, people have to eventually complement their knowledge using their own experience filling in the blanks from what little has been said. Thus, this research aims to identify which are the particular social messages associated with the easing or inhibition of sexual pleasure. Three hundred Mexican men and women ages 25 to 35 years old answered a self-report survey composed by the Inventory of facilitators and inhibitors of sexual pleasure and the Sexual premises questionnaire via pencil-paper and online. Results show a high endorsement to double standard messages associated with higher levels of sexual pleasure inhibitors like feeling pressured to have sexual activity, guilt and inability to reach orgasm, in contrast with people who endorse more permissive norms and beliefs, feeling connected to their sexual partners and confident with themselves. These results illustrate that the shaping of sexuality, from experience to society, is comprised of an important relationship between culture and sexual pleasure.

Keywords: culture, sexual double standard, sexual norms and beliefs, sexual pleasure

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Authors: F. Javier Benitez, Francisco J. Real, Juan Luis Acero, Francisco Casas

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Three emerging contaminants (amitriptyline hydrochloride, methyl salicylate and 2-phenoxyethanol) frequently found in waste-waters were selected to be individually degraded in ultra-pure water by the combined advanced oxidation process constituted by UV radiation and chlorine. The influence of pH, initial chlorine concentration and nature of the contaminants was firstly explored. The trend for the reactivity of the selected compounds was deduced: amitriptyline hydrochloride > methyl salicylate > 2-phenoxyethanol. A later kinetic study was carried out and focused on the specific evaluation of the first-order rate constants and the determination of the partial contribution to the global reaction of the direct photochemical pathway and the radical pathway. A comparison between the rate constant values among photochemical experiments without and with the presence of Cl₂ reveals a clear increase in the oxidation efficiency of the combined process with respect to the photochemical reaction alone. In a second stage, the simultaneous oxidation of mixtures of the selected contaminants in several types of water (ultrapure water, surface water from a reservoir, and two secondary effluents) was also performed by the same combination UV/Cl₂ under more realistic operating conditions. The efficiency of this combined system UV/Cl₂ was compared to other oxidants such as the UV/S₂O₈^2- and UV/H₂O₂ AOPs. Results confirmed that the UV/Cl₂ system provides higher elimination efficiencies among the AOPs tested.

Keywords: emerging contaminants, UV/chlorine advanced oxidation process, amitriptyline, methyl salicylate, 2-phenoxyethanol, chlorination, photolysis

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Authors: Suthida Panwong, Jeeraporn Pekkoh, Yingmanee Tragoolpua, Aussara Panya

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Dengue virus (DENV) infection is a major public health problem in many countries, especially in tropical and subtropical countries. DENV infection causes dengue fever that can progress to serious conditions of dengue hemorrhagic fever (DHF) or dengue shock syndrome (DSS), relevant to a high risk of mortality. However, there are no effective treatments available against the manifestation and fatalities. Currently, natural extracts have been widely used for the treatment of infectious diseases due to their safety, non-accumulation in the body, or lower side effects. Chlorella spp. is a microalgae with anti-viral activity, but there is not much report to support its ability to inhibit DENV infection. Thus, this study aimed to investigate the inhibitory effect of ethanolic extract from Chlorella sp. AARL G049, which was explored in Thailand on inhibition of DENV-2 infection. The inhibitory effect on viral infection was assessed using a foci-forming assay (FFA), which revealed that a concentration of 125 µg/mL could inhibit viral infection in Vero cells by 75.45±8.06% when treated at the same time as DENV-2 infection. Moreover, the extract at an equal concentration effectively reduced viral protein synthesis by 90.51±5.48% when assessed in human cell lines using enzyme-linked immunosorbent assay (ELISA). Concordantly, the number of infected cells after treatment was reduced as measured by immunofluorescent assay (IFA). Therefore, the finding of this study supports the potential use of Chlorella sp. extract to suppress DENV infection.

Keywords: viral infection, flavivirus, treatment, natural extract

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Authors: Mohammed M. Mahdy Tawfeek

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Objective: The aim of this work is to compare the outcome of photoactivated chromophore for keratitis-cross linking (PACK-CXL) window absorption (WA) alone with combined PACK-CXL WA and standard anti-microbial therapy (SAT) for the treatment of infectious keratitis. Patients and Methods: This is a randomized prospective comparative clinical trial. Thirty eyes with clinically suspected infectious keratitis were randomly assigned into two equal groups of 15 eyes each: Group (A) was treated by PACK-CXL WA alone and group (B) was treated by PACK-CXL WA combined with SAT. Identification of organisms was made by lab study before treatment. Corneal healing was evaluated by corneal examination and anterior segment OCT (AS-OCT). Written informed consent was obtained from all participants and the study was approved by the research ethics committee of the Faculty of Medicine, Zagazig University. The work has been carried out in accordance with The Code of Ethics of the World Medical Association (Declaration of Helsinki) for studies involving humans. Results: Complete healing and resolution (Successful treatment) were observed in 10 eyes (66.7%) of a group (A) and 14 eyes (93.3%) of group (B) and failure was observed in 5 eyes (33.3%) of a group (A) and one eye (6.67%) of group (B). They were statistically significant (P =0.042 and 0.003) in a comparison between both groups regarding success and failure of treatment, respectively. Complete corneal healing was reported in the third month postoperatively in 10 eyes (66.7%) of group (A) and 14 eyes (93.3%) of group (B). Complications were absent in 12 patients (80%) in group (A) and 14 patients (93.3%) of group (B); however, perforation and impending perforation were found in 3 patients of group (A) and only one patient of group (B). Conclusion: PACK-CXL is a promising, non-invasive treatment option for infectious keratitis, especially when performed with the window absorption (WA) technique, either alone or combined with SAT. It has a synergistic effect with a standard antimicrobial treatment that gives good outcome results in the treatment of infectious keratitis. Also, it avoids the antibiotics resistance that has become rapidly spreading worldwide.

Keywords: corneal cross linking, infectious keratitis, PACK-CXL, window absorption

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Authors: Ziani Borhane Eddine Cherif, Hazzi Mohamed, Mouhouche Fazia

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The vegetal extracts of aromatic and medicinal plants start to have much of interest like potential sources of natural bioactive molecules. Many features are conferred by the nature of the chemical function of their major constituents (phenol, alcohol, aldehyde, cetone). This biopotential lets us to focalize on the study of three main biological activities, the antioxidant, antibiotic and insecticidal activities of six Algerian aromatic plants in the aim of making in evidence by the chromatographic analysis (CPG and CG/SM) the phytochemical compounds implicating in this effects. The contents of Oxygenated monoterpenes represented the most prominent group of constituents in the majority of plants. However, the α-Terpineol (28,3%), Carvacrol (47,3%), pulégone (39,5%), Chrysanthenone (27,4%), Thymol 23,9%, γ-Terpinene 23,9% and 2-Undecanone(94%) were the main components. The antioxyding activity of the Essential oils and no-volatils extracts was evaluated in vitro using four tests: inhibition of free radical 2,2-diphenyl-1-picrylhydrazyl (DPPH) and the 2,2-Azino-bis (3-ethylbenzthiazoline-6-sulphonic acid) radical-scavenging activity (ABTS•+), the thiobarbituric acid reactive substances (TBARS) assays and the reducing power. The measures of the IC50 of these natural compounds revealed potent activity (between 254.64-462.76mg.l-1), almost similar to that of BHT, BHA, Tocopherol and Ascorbic acid (126,4-369,1 mg.l-1) and so far than the Trolox one (IC50= 2,82mg.l-1). Furthermore, three ethanol extracts were found to be remarkably effective toward DPPH and ABTS inhibition, compared to chemical antioxidant BHA and BHT (IC = 9.8±0.1 and 28±0.7 mg.l-1, respectively); for reducing power test it has also exhibited high activity. The study on the insecticidal activity effect by contact, inhalation, fecundity and fertility of Callosobruchus maculatus and Tribolium confusum showed a strong potential biocide reaching 95-100% mortality only after 24 hours. The antibiotic activity of our essential oils were evaluated by a qualitative study (aromatogramme) and quantitative (MIC, MBC and CML) on four bacteria (Gram+ and Gram-) and one strain of pathogenic yeast, the results of these tests showed very interesting action than that induced by the same reference antibiotics (Gentamycin, and Nystatin Ceftatidine) such that the inhibition diameters and MIC values for tested microorganisms were in the range of 23–58 mm and 0.015–0.25%(v/v) respectively.

Keywords: aromatic plants, essential oils, no-volatils extracts, bioactive molecules, antioxidant activity, insecticidal activity, antibiotic activity

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Authors: Sarah Crawford, Gerry Lesley

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This research is a pre-clinical assessment of anti-cancer effects of novel non-steroidal diethyl stilbestrol-like estrogen analogs in estrogen-receptor positive/ progesterone-receptor positive human breast cancer microtumors of MCF 7 cell line. Tamoxifen analog formulation (Tam A1) was used as a single agent or in combination with therapeutic concentrations of 4-hydroxytamoxifen, currently used as a long-term treatment for the prevention of breast cancer recurrence in women with estrogen receptor positive/ progesterone receptor positive malignancies. At concentrations ranging from 30-50 microM, Tam A1 induced microtumor disaggregation and cell death. Incremental cytotoxic effects correlated with increasing concentrations of Tam A1. Live tumor microscopy showed that microtumos displayed diffuse borders and substrate-attached cells were rounded-up and poorly adherent. A complete cytotoxic effect was observed using 40-50 microM Tam A1 with time course kinetics similar to 4-hydroxytamoxifen. Combined treatment with TamA1 (30-50 microM) and 4-hydroxytamoxifen (10-15 microM) induced a highly cytotoxic, synergistic combined treatment response that was more rapid and complete than using 4-hydroxytamoxifen as a single agent therapeutic. Microtumors completely dispersed or formed necrotic foci indicating a highly cytotoxic combined treatment response. Moreover, breast cancer microtumors treated with both 4-hydroxytamoxifen and Tam A1 displayed lower levels of long-term post-treatment regrowth, a critical parameter of primary drug resistance, than observed for 4-hydroxytamoxifen when used as a single agent therapeutic. Tumor regrowth at 6 weeks post-treatment with either single agent 4-hydroxy tamoxifen, Tam A1 or a combined treatment was assessed for the development of drug resistance. Breast cancer cells treated with both 4-hydroxytamoxifen and Tam A1 displayed significantly lower levels of post-treatment regrowth, indicative of decreased drug resistance, than observed for either single treatment modality. The preclinical data suggest that combined treatment involving the use of tamoxifen analogs may be a novel clinical approach for long-term maintenance therapy in patients with estrogen-receptor positive/progesterone-receptor positive breast cancer receiving hormonal therapy to prevent disease recurrence. Detailed data on time-course, IC50 and tumor regrowth assays post- treatment as well as a proposed mechanism of action to account for observed synergistic drug effects will be presented.

Keywords: 4-hydroxytamoxifen, tamoxifen analog, drug-resistance, microtumors

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