Search results for: heterogeneous cells

Authors: Sonal Tuljaram Kame

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Growth and development is based on proper diet. A balanced diet contains all the nutrients in required quantum. Although physical growth is completed by young adulthood, the body tissues remain in a dynamic state with catabolism slightly exceeding anabolism, resulting in a net decrease in the number of cells. After the years of adolescence which cause upheavals in the life of the person, the individual struggle to emerge as an adult who know who he is and what his goals are. During this period nutrients are needed for maintaining the health and energy is required for physical functions and physical activities. The nutritional requirement in young adulthood differs from other periods of life. Iron is needed for haemoglobin synthesis and necessitates by the considerable examination of blood volume. Young adult girls need to ensure adequate intake of iron as they loose 0.5 mg/day by way of menstruation. This is complete awareness about nutritional and health on the other side there is widespread ignorance about nutrition and health among young adult girls. The young adult girls who are aware about nutrition and health seem to be very conscious about nutritional intake and health. Figure consciousness and fear of obesity leads to self imposed intake of nutrients. It may result in various health problems. The study was planned to investigate nutrient intake, find relation between nutritional intake, clinical examination score and health status of young adult girls. The present study is based on the data collected from 120 young adult girls studying in four different competitive exams coaching academies in Akola city of Maharashtra. It was found that nutritional intake of these young adult girls was below the recommended level, nutritional knowledge level and nutritional intake are associated attributes, calories, calcium and protein intake is positively correlated with clinical examination and health status. It was concluded that well planned nutritional counseling for the young adult girls can help prevent nutritional deficiency diseases and disorders which may lead to anaemic condition in young adult girls. Girls need to be educated on intake of iron and vitamin B12.

Keywords: nutritional intake, health status, young adult girls, correlation studies

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Authors: Houda Haddad, Nolwen Jouvenet, Maxime Chazal, Frédéric Tangy, Amira Zairi

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Zika virus represents the primary cause of infection during pregnancy and can lead to various neurological disorders, such as microcephaly and Guillain-Barré syndrome, affecting both children and adults. This infection is also associated with urological and nephrological problems. So far, evidence of mosquito-borne Zika virus infection has been reported in a total of 89 countries and territories. However, surveillance efforts primarily concentrate on outbreaks that this virus can cause, yet the measures implemented are typically limited. Currently, there are no specific treatments or vaccines designed for the prevention or treatment of Zika virus infection or its associated disease. The development of effective therapeutic agents presents an urgent need. Importantly, an alternative for advancing the discovery of molecules could be dermaseptins, a family of antimicrobial peptides known for their potential antiviral properties. In this study, we carried out the synthesis of dermaseptins and their analogs and subsequently assessed the bioactivity tests against Zika virus (ZIKV PF13) of dermaseptins B2 and S4 and their derivatives. The cytotoxicity of these peptides was investigated on the HMC3 cell line and HeLa cells by CellTiter-Glo® Luminescent Cell Viability Assay. Thereafter, we evaluated the antiviral activity caused by the action of our dermaseptins on the viral envelope using the Fluorescence Activated Cell Sorting (FACS). The cytotoxicity of our molecules was concentration-dependent at microgram concentrations except for dermaseptin B2 and its derivative, which present no toxicity against HeLa and HMC3 cell lines. It was observed that all tested analogs from the S4 family exhibited antiviral activity with low concentrations ranging from 3 to 12.5 μg/mL, unlike the native B2 and its derivative, which increased the infectivity. Pre-incubating of dermaseptins with ZIKV PF13 before infection revealed that these derivatives inhibit the initial stages of virus infection. In summary, these results suggest that dermaseptins could serve as lead structures for the development of potent antiviral agents against Zika virus infections.

Keywords: dermaseptin B2, dermaseptin S4, analogs, zika virus, neurological infections, antiviral activity

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Authors: Małgorzata Tomczyńska, Joanna Saluk-Bijak

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Background: Graves’ disease is a frequent organ-specific autoimmune thyroid disease, which characterized by the presence of different kind autoantibodies, that, in most cases, act as agonists of the thyrotropin receptor, leading to hyperthyroidism. Role of platelets and lymphocytes can be modulated in the pathophysiology of thyroid autoimmune diseases. Interference in the physiology of platelets can lead to enhanced activity of these cells. Activated platelets can bind to circulating lymphocytes and to affect lymphocyte adhesion. Platelets and lymphocytes can regulate mutual functions. Therefore, the activation of T lymphocytes, as well as blood platelets, is associated with the development of inflammation and oxidative stress within the target tissue. The present study was performed to investigate a platelet-lymphocyte relation by assessing the degree of their mutual aggregation in whole blood of patients with Graves’ disease. Also, the purpose of this study was to examine the impact of platelet interaction on lymphocyte migration capacity. Methods: 30 patients with Graves’ disease were recruited in the study. The matched 30 healthy subjects were served as the control group. Immunophenotyping of lymphocytes was carried out by flow cytometry method. A CytoSelect™ Cell Migration Assay Kit was used to evaluate lymphocyte migration and adhesion to blood platelets. Visual assessment of lymphocyte-platelet aggregate morphology was done using confocal microscope after magnetic cell isolation by Miltenyi Biotec. Results: The migration and functional responses of lymphocytes to blood platelets were greater in the group of Graves’ disease patients compared with healthy controls. The group of Graves’ disease patients exhibited a reduced T lymphocyte and a higher B cell count compared with controls. Based on microscopic analysis, more platelet-lymphocyte aggregates were found in patients than in control. Conclusions: Studies have shown that in Graves' disease, lymphocytes show increased platelet affinity, more strongly migrating toward them, and forming mutual cellular conglomerates. This may be due to the increased activation of blood platelets in this disease.

Keywords: blood platelets, cell migration, Graves’ disease, lymphocytes, lymphocyte-platelet aggregates

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Authors: Yemima Dani Riani, Anggraini Barlian

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Green turtle (Chelonia mydas) is one of well known long-lived turtle. Its age can reach 100 years old. Senescence in green turtle is an interesting process to study because until now no clear explanation has been established about senescence at cellular or molecular level in this species. Since 1999, green turtle announced as an endangered species. Hence, establishment of fibroblast skin cell culture of green turtle may be material for future study of senescence. One common marker used for detecting senescence is telomere shortening. Reduced telomerase activity, the reverse transcriptase enzyme which adds TTAGGG DNA sequence to telomere end, may also cause senescence. The purpose of this research are establish and identify green turtle fibroblast skin cell culture and also compare telomere length and telomerase activity from passage 5 and 14. Primary cell culture made with primary explant method then cultured in Leibovitz-15 (Sigma) supplemented by 10% Fetal Bovine Serum (Sigma) and 100 U/mL Penicillin/Streptomycin (Sigma) at 30 ± 1oC. Cells identified with Rabbit Anti-Vimentin Polyclonal Antibody (Abcam) and Goat Polyclonal Antibody (Abcam) using confocal microscope (Zeiss LSM 170). Telomere length obtained using TeloTAGGG Telomere Length Assay (Roche) while telomerase activity obtained using TeloTAGGG Telomerase PCR ElisaPlus (Roche). Primary cell culture from green turtle skin had fibroblastic morphology and immunocytochemistry test with vimentin antibody proved the culture was fibroblast cell. Measurement of telomere length and telomerase activity showed that telomere length and telomerase activity of passage 14 was greater than passage 5. However, based on morphology, green turtle fibroblast skin cell culture showed senescent morphology. Based on the analysis of telomere length and telomerase activity, suspected fibroblast skin cell culture of green turtles is not undergo aging through telomere shortening.

Keywords: cell culture, chelonia mydas, telomerase, telomere, senescence

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Authors: Waddah Abdullah, Saleh Al-Sarem

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Electrokinetic remediation was undoubtedly proven to be one of the most efficient techniques used to clean up soils contaminated with polar charged contaminants (such as heavy metals) and non-polar organic contaminants. It can be efficiently used to clean up low permeability mud, wastewater, electroplating wastes, sludge, and marine dredging. This study presented and discussed the results of electrokinetic remediation processes to clean up soils contaminated with nickel. Two types of electrokinetics cells were used: an open cell and an advanced cylindrical cell. Two types of soils were used for this investigation; the Azraq green clay which has very low permeability taken from the eastern part of Jordan (city of Azraq) and a sandy soil having, relatively, very high permeability. The clayey soil was spiked with 500 ppm of nickel, and the sandy soil was spiked with 1500 ppm of nickel. Fully saturated and partially saturated clayey soils were used for the clean-up process. Clayey soils were tested under a direct current of 80 mA and 50 mA to study the effect of the electrical current on the remediation process. Chelating agent (Na-EDTA), disodium ethylene diamine tetraacetatic acid, was used in both types of soils to enhance the electroremediation process. The effect of carbonates presence in the contaminated soils, also, was investigated by use of sodium carbonate and calcium carbonate. pH changes in the anode and the cathode compartments were controlled by use of buffer solutions. The results of the investigation showed that for the fully saturated clayey soil spiked with nickel had an average removal efficiency of 64%, and the average removal efficiency was 46% for the unsaturated clayey soil. For the sandy soil, the average removal efficiency of Nickel was 90%. Test results showed that presence of carbonates in the remediated soils retarded the clean-up process of nickel-contaminated soils (removal efficiency was reduced from 90% to 60%). EDTA enhanced decontamination of nickel contaminated clayey and sandy soils with carbonates was studied. The average removal efficiency increased from 60% (prior to using EDTA) to more than 90% after using EDTA.

Keywords: buffer solution, EDTA, electroremediation, nickel removal efficiency

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Authors: Biva Samadder, Samita Manna

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India is a melting pot of races, tribes, castes and communities. The population of India can be roughly branched into the huge majority of “Civilized” Indians of the Plains and the minority of Tribal population of the hill area and the forest who constituting almost 16 percent of total population of India. The Kirat community composed of four ethnic tribes: Limbu, Lepcha, Dhimal, and Rai. These Kirat people were found to be rich in indigenous knowledge, skill and practices especially for the use on medicinal plants and livelihood purposes. The “Mundhum" is the oral scripture or the “Bible of the Limbus” which serves as the canon of the codes of the Limbu socialization, their moral values and the very orientation of their lifestyle. From birth till death the Limbus are disciplined in the life with full of religious rituals, traditions and culture governed by community norms with a rich legacy of indigenous knowledge and traditional practices. The present study has been conducted using both secondary as well as primary data by applying social methodology consisting of the social survey, questionnaire, interviews and observations in the Kalimpong Block-I of Darjeeling District of west Bengal of India, which is a heterogeneous zone in terms of its ethnic composition and where the Limbus are pre-dominantly concentrated. Due to their close contact with other caste and communities Limbus are now adjusted with the changing situation by borrowing some cultural traits from the other communities and changes that have taken place in their cultural practices, religious beliefs, economic aspects, languages and in social roles and relationships which is bringing the change in their material culture. Limbu language is placed in the Tibeto- Burman Language category. But due to the political and cultural domination of educationally sound and numerically dominant Bengali race, the different communities in this area forced to come under the one umbrella of the Nepali or Gorkhali nation (nation-people). Their respective identities had to be submerged in order to constitute as a strong force to resist Nepali domination and ensure their common survival. As Nepali is a lingua-franca of the area knowing and speaking Nepali language helps them in procuring economic and occupational facilities. Ironically, present day younger generation does not feel comfortable speaking in their own Limbu tongue. The traditional knowledge about medicinal plants, healing, and health culture is found to be wear away due to the lack of interest of young generation. Not only poverty, along with exclusion due to policies they are in the phase of extinction, but their capabilities are ignored and not documented and preserved especially in the case of Limbus who having a great cultural heritage of an oral tradition. Attempts have been made to discuss the persistence and changes in socioeconomic pattern of life in relation to the social structure, material culture, cultural practices, social relationships, indigenous technology, ethos and their values and belief system.

Keywords: changing social relationship, cultural transition, identity, indigenous knowledge, language

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Authors: Anastasia Constantinou, Stephen Morris

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Background: The adoption of synchronous and asynchronous telemedicine modalities for primary care consultations has exponentially increased since the COVID-19 pandemic. However, there is limited understanding of how virtual consultations influence healthcare resource utilization and other quality measures including safety, timeliness, efficiency, patient and provider satisfaction, cost-effectiveness and environmental impact. Aim: Quantify the rate of follow-up visits, emergency department visits, hospitalizations, request for investigations and prescriptions and comment on the effect on different quality measures associated with different telemedicine modalities used for primary care services and primary care referrals to secondary care Design and setting: Systematic review in primary care Methods: A systematic search was carried out across three databases (Medline, PubMed and Scopus) between August and November 2023, using terms related to telemedicine, general practice, electronic referrals, follow-up, use and efficiency and supported by citation searching. This was followed by screening according to pre-defined criteria, data extraction and critical appraisal. Narrative synthesis and metanalysis of quantitative data was used to summarize findings. Results: The search identified 2230 studies; 50 studies are included in this review. There was a prevalence of asynchronous modalities in both primary care services (68%) and referrals from primary care to secondary care (83%), and most of the study participants were females (63.3%), with mean age of 48.2. The average follow-up for virtual consultations in primary care was 28.4% (eVisits: 36.8%, secure messages 18.7%, videoconference 23.5%) with no significant difference between them or F2F consultations. There was an average annual reduction of primary care visits by 0.09/patient, an increase in telephone visits by 0.20/patient, an increase in ED encounters by 0.011/patient, an increase in hospitalizations by 0.02/patient and an increase in out of hours visits by 0.019/patient. Laboratory testing was requested on average for 10.9% of telemedicine patients, imaging or procedures for 5.6% and prescriptions for 58.7% of patients. When looking at referrals to secondary care, on average 36.7% of virtual referrals required follow-up visit, with the average rate of follow-up for electronic referrals being higher than for videoconferencing (39.2% vs 23%, p=0.167). Technical failures were reported on average for 1.4% of virtual consultations to primary care. When using carbon footprint estimates, we calculate that the use of telemedicine in primary care services can potentially provide a net decrease in carbon footprint by 0.592kgCO2/patient/year. When follow-up rates are taken into account, we estimate that virtual consultations reduce carbon footprint for primary care services by 2.3 times, and for secondary care referrals by 2.2 times. No major concerns regarding quality of care, or patient satisfaction were identified. 5/7 studies that addressed cost-effectiveness, reported increased savings. Conclusions: Telemedicine provides quality, cost-effective, and environmentally sustainable care for patients in primary care with inconclusive evidence regarding the rates of subsequent healthcare utilization. The evidence is limited by heterogeneous, small-scale studies and lack of prospective comparative studies. Further research to identify the most appropriate telemedicine modality for different patient populations, clinical presentations, service provision (e.g. used to follow-up patients instead of initial diagnosis) as well as further education for patients and providers alike on how to make best use of this service is expected to improve outcomes and influence practice.

Keywords: telemedicine, healthcare utilisation, digital interventions, environmental impact, sustainable healthcare

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Authors: Subodh Kumar, Sanjeev Kumar Sharma, Gaurav Kaushik, Pramod Avti, Phulen Sarma, Bikash Medhi, Krishan Lal Khanduja

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Background: It is well known that cigarette smoke is one of the causative factors in various lung diseases especially cancer. Carcinogens and oxidant molecules present in cigarette smoke not only damage the cellular constituents (lipids, proteins, DNA) but may also regulate the molecular pathways involved in inflammation and cancer. Continuous oxidative stress caused by the constituents of cigarette smoke leads to higher PhospholipaseA₂ (PLA₂) activity, resulting in elevated levels of secondary metabolites whose role is well defined in cancer. To reduce the burden of chronic inflammation as well as oxidative stress, and higher levels of secondary metabolites, we checked the curative potential of PLA₂ inhibitor Bromoenol Lactone (BEL) during continuous exposure of cigarette smoke condensate (CSC). Aim: To check the therapeutic potential of Bromoenol Lactone (BEL), an inhibitor of PhospholipaseA₂s, in pathways of CSC-induced changes in type I and type II alveolar epithelial cells. Methods: Effect of BEL on CSC-induced PLA2 activity were checked using colorimetric assay, cellular toxicity using cell viability assay, membrane integrity using fluorescein di-acetate (FDA) uptake assay, reactive oxygen species (ROS) levels and apoptosis markers through flow cytometry, and cellular regulation using MAPKinases levels, in lung epithelium. Results: BEL significantly mimicked CSC-induced PLA₂ activity, ROS levels, apoptosis, and kinases level whereas improved cellular viability and membrane integrity. Conclusions: Current observations revealed that BEL may be a potential therapeutic agent during Cigarette smoke-induced anomalies in lung epithelium.

Keywords: cigarette smoke condensate, phospholipase A₂, oxidative stress, alveolar epithelium, bromoenol lactone

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Authors: Mansouri Ouarda, Abdennour Cherif, Saidi Malika

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Since the industrial revolution, many anthropogenic activities have caused environmental, considerable and overall changes. The lead represents a very dangerous disruptive for the functioning of the body. In this context the current study aims at evaluating a natural therapy by the use of the plant grass in wheat (Triticum durum) against the toxicity of lead in rat wistar male. The rats were divided into three groups: the control group, the group treated with 600 mg /kg food of lead only (Pb) is the group treated with the combination of 600 mg/kg of food and 9g/rat /day of the plant grass in wheat (Pb-bl). The duration of the treatment is 6 weeks. The results of the biometrics of the organs (thyroid, kidney, testis and epididymis) show no significant difference between the three groups. The dosage of a few parameters and hormonal biochemical shows a decrease in the concentration of the hormone T3 and TSH levels among the group pb alone compared to the control and Pb-Bl. These results have been confirmed by the study of histological slices. A morphological changes represented by a shrinking volume of vesicles with the group treated with Pb alone. A return to the normal state of the structure of the follicles was observed. The concentration in serum testosterone, urea and creatinine was significantly increased among the group treated by Pb only in relation to the control and Pb-Bl. whereas the rate of glucose did not show any significant difference. The histology study of the kidney, testis and epididymal weights show no modification at the group Pb-bl comparing to the control. The parenchyma of the kidney shows a dilation of tubes distal and proximal causing a tubular nephropathy for the batch processed by Pb only. The testicles have marked a destruction or absence of germ cells and the light of some seminiferous are almost empty. Conclusion: The supplementation of the plant Triticum durum has caused a considerable improvement which ensures the return of parameters investigated in the normal state.

Keywords: creatinine, glucose, histological sections, T3, TSH, testosterone

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Authors: Clara Franch de la Cal, Christopher J Morris, Michael McArthur

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Cystic fibrosis (CF) is an autosomal recessive genetic disorder characterized by abnormal transport of chloride and sodium across the lung epithelium, leading to thick and viscous secretions. Within which CF patients suffer from repeated bacterial pulmonary infections, with Pseudomonas aeru-ginosa (PA) eliciting the greatest inflammatory response, causing an irreversible loss of lung func-tion that determines morbidity and mortality. The cell wall of PA is a permeability barrier to many antibacterials and the rise of Mutli-Drug Resistant strains (MDR) is eroding the efficacy of the few remaining clinical options. In addition when PA infection becomes established it forms an antibi-otic-resistant biofilm, embedded in which are slow growing cells that are refractive to drug treat-ment. Making the development of new antibacterials a major challenge. This work describes the development of new type of nanoparticulate oligonucleotide antibacterial capable of tackling PA infections, including MDR strains. It is being developed to both block growth and prevent biofilm formation. These oligonucleotide therapeutics, Transcription Factor Decoys (TFD), act on novel genomic targets by capturing key regulatory proteins to block essential bacterial genes and defeat infection. They have been successfully transfected into a wide range of pathogenic bacteria, both in vitro and in vivo, using a proprietary delivery technology. The surfactant used self-assembles with TFD to form a nanoparticle stable in biological fluids, which protects the TFD from degradation and preferentially transfects prokaryotic membranes. Key challenges are to adapt the nanoparticle so it is active against PA in the context of biofilms and to formulate it for administration by inhalation. This would allow the drug to be delivered to the respiratory tract, thereby achieving drug concentrations sufficient to eradicate the pathogenic organisms at the site of infection.

Keywords: antibacterials, transcriptional factor decoys (TFDs), pseudomonas aeruginosa

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Authors: Umar Saeed

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Peptidyl-prolyl cis/trans isomerases Par14 and Par17 in humans play crucial roles in diverse cellular processes, including protein folding, chromatin remodeling, DNA binding, ribosome biogenesis, and cell cycle progression. However, the effects of Par14 and Par17 on viral replication have been explored to a limited extent. We first time discovered their influential roles in promoting Hepatitis B Virus replication. In this study, we observed that in the presence of HBx, either Par14 or Par17 could upregulate HBV replication. However, in the absence of HBx, neither Par14 nor Par17 had any effect on replication. Their mechanism of action involves binding to specific motifs within HBc and HBx proteins. Notably, they target the conserved 133Arg-Pro134 (RP) motif of HBc and the 19RP20-28RP29 motifs of HBx. This interaction is fundamental for the stability of HBx, core particles, and HBc. Par14 and Par17 exhibit versatility by binding both outside and inside core particles, thereby facilitating core particle assembly through their participation in HBc dimer-dimer interactions. NAGE and immunoblotting analyses unveiled the binding of Par14/Par17 to core particles. Co-immunoprecipitation experiments further demonstrated the interaction of Par14/Par17 with core particle assembly-defective and dimer-positive HBc-Y132A. It's essential to emphasize that R133 is the key residue in the HBc RP motif that governs their interaction with Par14/Par17. Chromatin immunoprecipitation conducted on HBV-infected cells elucidated the participation of residues S19 and E46/D74 in Par14 and S44 and E71/D99 in Par17 in the recruitment of 133RP134 motif-containing HBc into cccDNA. Depleting PIN4 in liver cell lines results in a significant reduction in cccDNA levels, pgRNA, sgRNAs, HBc, core particle assembly, and HBV DNA synthesis. Notably, parvulin inhibitors like juglone and PiB have proven to be effective in substantially reducing HBV replication. These inhibitors weaken the interaction between HBV core particles and Par14/Par17, underscoring the dynamic nature of this interaction. It's also worth noting that specific Par14/Par17 inhibitors hold promise as potential therapeutic options for chronic hepatitis B.

Keywords: Par14Par17, HBx, HBc, cccDNA, HBV

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Authors: Howaida I. Abd-Alla, Omnia Kutkat, Yassmin Moatasim, Magda T. Ibrahim, Marwa A. Mostafa, Mohamed GabAllah, Mounir M. El-Safty

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Artemisia judaica (known shih-balady), Azadirachta indica and Sophora tomentosa (known yellow necklace pod) are members of available medicinal plants well-known for their traditional medical use in Egypt which suggests that they probably harbor broad-spectrum antiviral, immunostimulatory and anti-inflammatory functions. Their ethyl acetate-dichloromethane (1:1, v/v) extracts were evaluated for the potential anti-Middle East respiratory syndrome-related coronavirus (anti-MERS-CoV) activity. Their cytotoxic activity was tested in Vero-E6 cells using 3-(4,-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method with minor modification. The plot of percentage cytotoxicity for each extract concentration has calculated the concentration which exhibited 50% cytotoxic concentration (TC50). A plaque reduction assay was employed using safe dose of extract to evaluate its effect on virus propagation. The highest inhibition percentage was recorded for the yellow necklace pod, followed by Shih-balady. The possible mode of action of virus inhibition was studied at three different levels viral replication, viral adsorption and virucidal activity. The necklace pod leaves have induced virucidal effects and direct effects on the replication of virus. Phytochemical investigation of the promising necklace pod led to the isolation and structure determination of nine compounds. The structure of each compound was determined by a variety of spectroscopic methods. Compounds 4-O-methyl sorbitol 1, 8-methoxy daidzin 6 and 6-methoxy apigenin-7-O-β-D-glucopyranoside 8 were isolated for the first time from the Sophora genus and the other six compounds were the first time that they were isolated from this species according to available works of literature. Generally, the highest anti-CoV 2 activity of S. tomentosa was associated with the crude ethanolic extract, indicating the possibility of synergy among the antiviral phytochemical constituents (1-9).

Keywords: coronavirus, MERS-CoV, mode of action, necklace pod, shih-balady

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Authors: Anna Pick Kiong Ling, Jia May Chin, Rhun Yian Koh, Ying Pei Wong

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Background: Uncontrolled inflammation may cause serious inflammatory diseases if left untreated. Non-steroidal anti-inflammatory drug (NSAIDs) is commonly used to inhibit pro-inflammatory enzymes, thus, reduce inflammation. However, long term administration of NSAIDs leads to various complications. Medicinal plants are getting more attention as it is believed to be more compatible with human body. One of them is a flavonoid-containing medicinal plants, Strobilanthes crispus which has been traditionally claimed to possess anti-inflammatory and antioxidant activities. Nevertheless, its anti-inflammatory activities are yet to be scientifically documented. Objectives: This study aimed to examine the anti-inflammatory activity of S. crispus by investigating its effects on intracellular oxidative stress and prostaglandin E₂ (PGE₂) levels. Materials and Methods: In this study, the Maximum Non-toxic Dose (MNTD) of methanol extract of both leaves and stems of S. crispus was first determined using 3-(4,5-dimethylthiazolyl-2)-2,5-diphenytetrazolium Bromide (MTT) assay. The effects of S. crispus extracts at MNTD and half MNTD (½MNTD) on intracellular ROS as well as PGE₂ levels in 1.0 µg/mL LPS-stimulated RAW 264.7 macrophages were then be measured using DCFH-DA and a competitive enzyme immunoassay kit, respectively. Results: The MNTD of leaf extract was determined as 700µg/mL while for stem was as low as 1.4µg/mL. When LPS-stimulated RAW 264.7 macrophages were subjected to the MNTD of S. crispus leaf extract, both intracellular ROS and PGE₂ levels were significantly reduced. In contrast, stem extract at both MNTD and ½MNTD did not significantly reduce the PGE₂ level, but significantly increased the intracellular ROS level. Conclusion: The methanol leaf extract of S. crispus may possess anti-inflammatory properties as it is able to significantly reduce the intracellular ROS and PGE₂ levels of LPS-stimulated cells. Nevertheless, further studies such as investigating the interleukin, nitric oxide and cytokine tumor necrosis factor-α (TNFα) levels has to be conducted to further confirm the anti-inflammatory properties of S. crispus.

Keywords: anti-inflammatory, natural products, prostaglandin E2, reactive oxygen species

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Authors: Chiara Colarusso, Michela Terlizzi, Aldo Pinto, Rosalinda Sorrentino

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Cigarette smoking is the main cause and the most common risk factor for both COPD and lung cancer. In our previous studies, we proved that caspase-11 in mice and its human analogue, caspase-4, are involved in lung carcinogenesis and that AIM2 inflammasome might play a pro-cancerous role in lung cancer. Therefore, the aim of this study was to investigate potential crosstalk between COPD and lung cancer, focusing on AIM2 and caspase-11-dependent inflammasome signaling pathway. To mimic COPD, we took advantage of an experimental first-hand smoking mouse model and, to confirm what was observed in mice, we used human samples of lung adenocarcinoma patients stratified according to the smoking and COPD status. We demonstrated that smoke exposure led to emphysema-like features, bronchial tone impairment, and release of IL-1-like cytokines (IL-1α, IL-1β, IL-33, IL-18) in a caspase-1 independent manner in C57Bl/6N. Rather, a dysfunctional caspase-11 in smoke-exposed 129Sv mice was associated to lower bronchial inflammation, collagen deposition, and IL-1-like inflammation. In addition, for the first time, we found that AIM2 inflammasome is involved in lung inflammation in smoking and COPD, in that its expression was higher in smoke-exposed C57Bl/6N compared to 129Sv smoking mice, who instead did not show any alteration of AIM2 in both macrophages and dendritic cells. Moreover, we found that AIM2 expression in the cancerous tissue, albeit higher than non-cancerous tissue, was not statistically different according to the COPD and smoking status. Instead, the higher expression of AIM2 in non-cancerous tissue of smoker COPD patients than smokers who did not have COPD was correlated to a higher hazard ratio of poor survival rate than patients who presented lower levels of AIM2. In conclusion, our data highlight that caspase-11 in mice is associated to smoke-induced lung latent inflammation which could drive the establishment of lung cancer, and that AIM2 inflammasome plays a role at the crosstalk between smoking/COPD and lung adenocarcinoma in that its higher presence is correlated to lower survival rate of smoker COPD adenocarcinoma.

Keywords: COPD, inflammasome, lung cancer, lung inflammation, smoke

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Authors: Gerhardt Boukes, Maryna Van De Venter, Sharlene Govender

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Macrofungi have been used for the past two thousand years in Asian countries, and more recently in Western countries, for their medicinal properties. Biological activities include antimicrobial, antioxidant, anti-inflammatory, antidiabetic, anticancer and immunomodulatory to name a few. Several biologically active compounds have been identified and isolated. Macrofungal research in Africa is poorly documented and to the best of our knowledge non-existent. South Africa has a rich macrofungal biodiversity, which includes endemic and exotic macrofungal species. Ethanolic extracts of 13 macrofungal species, including mushrooms, bracket fungi and puffballs, were prepared and screened for cytotoxicity against a panel of seven cell lines, including A549 (human lung adenocarcinoma), HeLa (human cervical adenocarcinoma), HT-29 (human colorectal adenocarcinoma), MCF7 (human breast adenocarcinoma), MIA PaCa-2 (human pancreatic ductal adenocarcinoma), PC-3 (human prostate adenocarcinoma) and Vero (African green monkey kidney epithelial) cells using MTT. Cell lines were chosen according to the most prevalent cancer types affecting males and females in South Africa and globally, and the mutations they contain. Preliminary results have shown that three of the macrofungal genera, i.e. Fomitopsis, Gymnopilus and Pycnoporus, have shown cytotoxic activity, ranging between IC50 ~20 and 200 µg/mL. The molecular mechanism of action contributing to cell death investigated and being investigated include apoptosis (i.e. DNA cell cycle arrest, caspase-3 activation and mitochondrial membrane potential), autophagy (i.e. acridine orange and LC3B staining) and ER stress (i.e. thioflavin T staining and caspase-12) in the presence of melphalan, chloroquine and thapsigargin/tuncamycin as positive controls, respectively. The genus, Pycnoporus, has shown the best cytotoxicity of the three macrofungal genera. Future work will focus on the identification and isolation of novel active compounds and elucidating the mechanism/s of action.

Keywords: cancer, cytotoxicity, macrofungi, mechanism/s of action

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Authors: Soledad Carinelli, Iñigo Fernández, José Luis González-Mora, Pedro A. Salazar-Carballo

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Mastitis is the most relevant inflammatory disease in cattle, affecting the animal health and causing important economic losses on dairy farms. This disease takes place in the mammary gland or udder when some opportunistic microorganisms, such as Staphylococcus aureus, Streptococcus agalactiae, Corynebacterium bovis, etc., invade the teat canal. According to the severity of the inflammation, mastitis can be classified as sub-clinical, clinical and chronic. Standard methods for mastitis detection include counts of somatic cells, cell culture, electrical conductivity of the milk, and California test (evaluation of “gel-like” matrix consistency after cell lysed with detergents). However, these assays present some limitations for accurate detection of subclinical mastitis. Currently, haptoglobin, an acute phase protein, has been proposed as novel and effective biomarker for mastitis detection. In this work, an electrochemical biosensor based on polydopamine-modified magnetic nanoparticles (MNPs@pDA) for haptoglobin detection is reported. Thus, MNPs@pDA has been synthesized by our group and functionalized with hemoglobin due to its high affinity to haptoglobin protein. The protein was labeled with specific antibodies modified with alkaline phosphatase enzyme for its electrochemical detection using an electroactive substrate (1-naphthyl phosphate) by differential pulse voltammetry. After the optimization of assay parameters, the haptoglobin determination was evaluated in milk. The strategy presented in this work shows a wide range of detection, achieving a limit of detection of 43 ng/mL. The accuracy of the strategy was determined by recovery assays, being of 84 and 94.5% for two Hp levels around the cut off value. Milk real samples were tested and the prediction capacity of the electrochemical biosensor was compared with a Haptoglobin commercial ELISA kit. The performance of the assay has demonstrated this strategy is an excellent and real alternative as screen method for sub-clinical bovine mastitis detection.

Keywords: bovine mastitis, haptoglobin, electrochemistry, magnetic nanoparticles, polydopamine

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Authors: Yasmin Begum Mohammed

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Ketorolac tromethamine (KTM) is a non-steroidal anti-inflammatory drug with a potent analgesic and anti-inflammatory activity due to prostaglandin related inhibitory effect of drug. It is a non-selective cyclo-oxygenase inhibitor. The drug is currently used orally and intramuscularly in multiple divided doses, clinically for the management arthritis, cancer pain, post-surgical pain, and in the treatment of migraine pain. KTM has short biological half-life of 4 to 6 hours, which necessitates frequent dosing to retain the action. The frequent occurrence of gastrointestinal bleeding, perforation, peptic ulceration, and renal failure lead to the development of other drug delivery strategies for the appropriate delivery of KTM. The ideal solution would be to target the drug only to the cells or tissues affected by the disease. Drug targeting could be achieved effectively by liposomes that are biocompatible and biodegradable. The aim of the study was to develop a parenteral liposome formulation of KTM with improved efficacy while reducing side effects by targeting the inflammation due to arthritis. PEG-anchored (stealth) and non-PEG-anchored liposomes were prepared by thin film hydration technique followed by extrusion cycle and characterized for in vitro and in vivo. Stealth liposomes (SLs) exhibited increase in percent encapsulation efficiency (94%) and 52% percent of drug retention during release studies in 24 h with good stability for a period of 1 month at -20°C and 4°C. SLs showed about maximum 55% of edema inhibition with significant analgesic effect. SLs produced marked differences over those of non-SL formulations with an increase in area under plasma concentration time curve, t₁/₂, mean residence time, and reduced clearance. 0.3% of the drug was detected in arthritic induced paw with significantly reduced drug localization in liver, spleen, and kidney for SLs when compared to other conventional liposomes. Thus SLs help to increase the therapeutic efficacy of KTM by increasing the targeting potential at the inflammatory region.

Keywords: biodistribution, ketorolac tromethamine, stealth liposomes, thin film hydration technique

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Authors: Ina Filkobski, Eran Shor

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This article explores how newspapers cover murder of women by family members and intimate partners. Three major Israeli newspapers were compared in order to analyse the coverage of Jewish and Arab victims and culprits and to examine whether and in what ways the media contribute to the construction of symbolic boundaries between minority and dominant social groups. A sample of some 459 articles that were published between 2013 and 2015 was studied using a systematic qualitative content analysis. Our findings suggest that the treatment of murder cases by the media varies according to the ethnicity of both victims and culprits. The murder of Jews by family members or intimate partners was framed as a shocking and unusual event, a result of the individual personality or pathology of the culprit. Conversely, when Arabs were the killers, murders were often explained by focusing on the culture of the ethnic group, described as traditional, violent, and patriarchal. In two-thirds of the cases in which Arabs were involved, so-called ‘honor killing’ or other cultural explanations were proposed as the motive for the murder. This was often the case even before a suspect was detected, while police investigation was at its very early stages, and often despite forceful denials from victims’ families. In case of Jewish culprits, more than half of the articles in our sample suggested mental disorder to explain the acts and cultural explanations were almost entirely absent. Beyond the emphasis on psychological vs. cultural explanations, newspaper articles also tend to provide much more detail about Jewish culprits than about Arabs. Such detailed examinations convey a desire to make sense of the event by understanding the supposedly unique and unorthodox nature of the killer. The detailed accounts were usually absent from the reports on Arab killers. Thus, even if reports do not explicitly offer cultural motivations for the murder, the fact that reports often remain laconic leaves people to draw their own conclusions, which would then be likely based on existing cognitive scripts and previous reports on family murders among Arabs. Such treatment contributes to the notion that Arab and Muslim cultures, religions, and nationalities are essentially misogynistic and adhere to norms of honor and shame that are radically different from those of modern societies, such as the Jewish-Israeli one. Murder within the family is one of the most dramatic occurrences in the social world, and in societies that see themselves as modern it is a taboo; an ultimate signifier of danger. We suggest that representations of murder provide a valuable prism for examining the construction of group boundaries. Our analysis, therefore, contributes to the scholarly effort to understand the creation and reinforcement of symbolic boundaries between ‘society’ and its ‘others’ by systematically tracing the media constructions of ‘otherness’. While our analysis focuses on Israel, studies on the United States, Canada, and various European countries with ethnically and racially heterogeneous populations, make it clear that the stigmatisation and exclusion of visible, religious, and language minorities are not unique to the Israeli case.

Keywords: comparative study of media coverege of minority and majority groups, construction of symbolic group boundaries, murder of women by family members and intimate partners, Israel, Jews, Arabs

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Authors: Jiangang Shen

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Olfactory dysfunction is a common symptom companied by anxiety- and depressive-like behaviors in depressive patients. Chronic stress triggers hormone responses and inhibits the proliferation and differentiation of neural stem cells (NSCs) in the hippocampus and subventricular zone (SVZ)-olfactory bulb (OB), contributing to depressive behaviors and olfactory dysfunction. However, the cellular signaling molecules to regulate chronic stress mediated olfactory dysfunction are largely unclear. Adaptor proteins containing the pleckstrin homology domain, phosphotyrosine binding domain, and leucine zipper motif (APPLs) are multifunctional adaptor proteins. Herein, we tested the hypothesis that APPL2 could inhibit hippocampal neurogenesis by affecting glucocorticoid receptor (GR) signaling, subsequently contributing to depressive and anxiety behaviors as well as olfactory dysfunctions. The major discoveries are included: (1) APPL2 Tg mice had enhanced GR phosphorylation under basic conditions but had no different plasma corticosterone (CORT) level and GR phosphorylation under stress stimulation. (2) APPL2 Tg mice had impaired hippocampal neurogenesis and revealed depressive and anxiety behaviors. (3) GR antagonist RU486 reversed the impaired hippocampal neurogenesis in the APPL2 Tg mice. (4) APPL2 Tg mice displayed higher GR activity and less capacity for neurogenesis at the olfactory system with lesser olfactory sensitivity than WT mice. (5) APPL2 negatively regulates olfactory functions by switching fate commitments of NSCs in adult olfactory bulbs via interaction with Notch1 signaling. Furthermore, baicalin, a natural medicinal compound, was found to be a promising agent targeting APPL2/GR signaling and promoting adult neurogenesis in APPL2 Tg mice and chronic corticosterone-induced depression mouse models. Behavioral tests revealed that baicalin had antidepressant and olfactory-improving effects. Taken together, APPL2 is a critical therapeutic target for antidepressant treatment.

Keywords: APPL2, hippocampal neurogenesis, depressive behaviors and olfactory dysfunction, stress

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Authors: Yong-Hui Zheng

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Viruses hijack host machineries to propagate and spread, which disrupts cellular homeostasis and activates various counteractive mechanisms. Infection of enveloped viruses is dependent on their fusion proteins, which bind to viral receptors to allow virus entry into cells. Fusion proteins are glycoproteins and expressed in the endoplasmic reticulum (ER) by hijacking the secretory pathway. Previously, we reported that Zaire ebolavirus (EBOV)-glycoprotein (GP) expression induces ER stress, and EBOV-GP is targeted by the calnexin cycle to macro-ER-phagy for degradation. We now report that expression of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/SARS2)-spike (S) protein also causes ER stress, and its expression is strongly downregulated by mannosidase alpha class 1B member 1 (MAN1B1), a class I α-mannosidase from the ER. MAN1B1 co-localizes with SARS2-S in the ER, and its downregulation of SARS2-S is blocked by inhibitors targeting lysosomes and autophagy, but not proteasomes, indicating SARS2-S degradation by autolysosomes. Notably, the SARS2-S degradation does not require the core autophagy machinery including ATG3, ATG5, ATG7, and phosphatidylinositol 3-kinase catalytic subunit type 3 (PI3KC3)/vacuolar protein sorting 34 (VPS34), and instead, it requires Beclin 1 (BECN1), a core component in the PI3KC3 complex. In addition, MAN1B1 does not trigger SARS2-S polyubiquitination, and consistently, the SARS2-S degradation does not require the autophagy receptor sequestosome 1 (SQSTM1)/p62. MAN1B1 also downregulates EBOV-GP similarly, but this degradation does not require BECN1. Collectively, we conclude that MAN1B1 downregulates viral fusions by micro-ER-phagy, and importantly, we have identified BECN1-dependent and BECN1-independent mechanisms for micro-ER-phagy.

Keywords: Micro-ER-phagy, reticulophagy, fusion proteins, ER stress

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Authors: Radmila Maksimovic, Sonja Ketin, Rade Biocanin, Jelena Maksimovic

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The abnormal conditions of life and work genetic factors often play a major role in incidence of diabetes-diabetes, heart disease and vascular disease, jaundice, and post traumatic stress. Trauma and post traumatic stress are most common in the displaced persons,and the focus of this paper is to shed light on this issue in former Yugoslavia, Yugoslavia and now in our country. This is caused by increased beta-cell sensitivity to viruses, the development of autoimmune antibodies against its own pancreascells, degenerative changes in cells that r esult in change of structure and insulin. In this paper, we dealt with traumatic events and long-term psycho social consequences for internally displaced persons, several years after displacement, and found a high level of PTSD symptoms. This stress is present in almost 1/3 of internally displaced persons, and every sixth person is suffering from PTSD in the past. Respondents generally suffer from symptoms of intrusion, but there was a large number of symptoms, avoidance and increased arousal. We also found that gender, age andeducation related to the symptoms. Females, and older respondents and internally displaced persons with lower levels of education how a higher level of PTSD symptoms, especially symptoms of intrusion and increase darousal. It is a highly traumatized sample in which more than 1/2 of respondents experienced more than three traumatic events in life,although the number of traumas experienced before, during and after the conflict varies.We found that during the war, internally displaced persons haveexperienced more traumatic events compared with the periodbefore and after the conflict. Trauma are different in type. No significant correlation between the number of experienced trauma and PTSD, suggesting that it is necessary to further study the structure of past traumas and the intermediary effects of certain risk factors and protective factors.

Keywords: living environment, displaced persons, jaundice, diabetes, trauma, diabetic hypertension, post-traumatic stress (PTSD), treatment

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Authors: Boor Singh Lalia, Yarjan Abdul Samad, Raed Hashaikeh

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Three different kinds of solid polymer electrolytes were prepared using polyethylene oxide (PEO) as a base polymer, networked cellulose (NC) as a physical support and LiClO4 as a conductive salt for the electrolytes. Networked cellulose, a modified form of cellulose, is a biodegradable and environmentally friendly additive which provides a strong fibrous networked support for structural stability of the electrolytes. Although the PEO/NC/LiClO4 electrolyte retains its structural integrity and mechanical properties at 100oC as compared to pristine PEO-based polymer electrolytes, it suffers from poor ionic conductivity. To improve the room temperature conductivity of the electrolyte, PEO is replaced by the polyethylene glycol (PEG) which is a liquid phase that provides high mobility for Li+ ions transport in the electrolyte. PEG/NC/LiClO4 shows improvement in ionic conductivity compared to PEO/NC/LiClO4 at room temperature, but it is brittle and tends to form cracks during processing. An advanced solid polymer electrolyte with optimum ionic conductivity and mechanical properties is developed by using a ternary system: TEGDME/PEO/NC+LiClO4. At room temperature, this electrolyte exhibits an ionic conductivity to the order of 10-5 S/cm, which is very high compared to that of the PEO/LiClO4 electrolyte. Pristine PEO electrolytes start melting at 65 °C and completely lose its mechanical strength. Dynamic mechanical analysis of TEGDME: PEO: NC (70:20:10 wt%) showed an improvement of storage modulus as compared to the pristine PEO in the 60–120 °C temperature range. Also, with an addition of NC, the electrolyte retains its mechanical integrity at 100 oC which is beneficial for Li-ion battery operation at high temperatures. Differential scanning calorimetry (DSC) and thermal gravimetry analysis (TGA) studies revealed that the ternary polymer electrolyte is thermally stable in the lithium ion battery operational temperature range. As-prepared polymer electrolyte was used to assemble LiFePO4/ TEGDME/PEO/NC+LiClO4/Li half cells and their electrochemical performance was studied via cyclic voltammetry and charge-discharge cycling.

Keywords: solid polymer electrolyte, ionic conductivity, mechanical properties, lithium ion batteries, cyclic voltammetry

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Authors: Sercan Altundemir, Pinar Eribol, A. Kerem Uguz

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Microfluidics systems allow many-large scale laboratory applications to be miniaturized on a single device in order to reduce cost and advance fluid control. Moreover, such systems enable to generate and control droplets which have a significant role on improved analysis for many chemical and biological applications. For example, they can be employed as the model for cells in microfluidic systems. In this work, the interfacial instability of two immiscible Newtonian liquids flowing in a microchannel is investigated. When two immiscible liquids are in laminar regime, a flat interface is formed between them. If a direct current electric field is applied, the interface may deform, i.e. may become unstable and it may be ruptured and form micro-droplets. First, the effect of thickness ratio, total flow rate, viscosity ratio of the silicone oil and ethylene glycol liquid couple on the critical voltage at which the interface starts to destabilize is investigated. Then the droplet sizes are measured under the effect of these parameters at various voltages. Moreover, the effect of total flow rate on the time elapsed for the interface to be ruptured to form droplets by hitting the wall of the channel is analyzed. It is observed that an increase in the viscosity or the thickness ratio of the silicone oil to the ethylene glycol has a stabilizing effect, i.e. a higher voltage is needed while the total flow rate has no effect on it. However, it is observed that an increase in the total flow rate results in shortening of the elapsed time for the interface to hit the wall. Moreover, the droplet size decreases down to 0.1 μL with an increase in the applied voltage, the viscosity ratio or the total flow rate or a decrease in the thickness ratio. In addition to these observations, two empirical models for determining the critical electric number, i.e., the dimensionless voltage and the droplet size and another model which is a combination of both models, for determining the droplet size at the critical voltage are established.

Keywords: droplet formation, electrohydrodynamics, microfluidics, two-phase flow

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Authors: Kahina Amal Djiar, Mouna Gharbi, Maha Messaoudene, Oumelkheir Chareb

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Over the last decade, Algerian authorities have implemented an ambitious program of urban renewal, which includes important relocation operations. The objectives behind such strategic interventions are on the one hand, to carry out an incremental approach aiming at eradicating precarious housing and on the other hand, to diversify alternative housing options for families requiring better living spaces. It is precisely for these same purposes that the Djenan el-Hassan and Carrières Jaubert estates, which are both located in Algiers, have undergone major urban transformations. These dwelling sites were built as part of the famous "Battle of Housing", which was launched by French colonial administration in the 1950s just before the independence of Algeria in 1962. Today, the Djenan el-Hassan estate is almost entirely demolished following the relocation of 171 families. The Carrières Jaubert estate, for its part, has seen two kinds of operations. The first has been shaped by a process of urban requalification and redevelopment, which allowed some of the residents to stay on site after the transformation of most housing cells into larger apartments. The second operation has required the relocation of over 300 families to entirely newly built dwellings. Such projects of urban renewal are supposed to create new opportunities, not only in terms of local urban development, but also in terms of social perspectives for those families who are involved, either directly or indirectly, in the process of relocation. In fact, the percentage of urban violence in Algiers has increased instead. Recent events in the newly built estates show that residents are repeatedly experiencing and even instigating episodes of brutality, hostility and aggression. The objective of this paper is to examine the causes that have engendered such rise in urban violence in newly built housing estates in Algiers. This paper aims to present the findings of a recent qualitative research and highlight the way that poorly designed neighbourhood, combined with a relocation process that leaves little room for community participation, create inevitably severe social tensions.

Keywords: relocation, social housing, violence, Algiers

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Authors: S. Sharma, Gaballa Aqeelah, Tawfig Alghbaili, Ali Elmessmari

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There were abrupt discontinuities in the Brute Stack in the northernmost locations during the acquisition of 2D (2007) and 3D (2021) seismic data in the northwest region of the Ghadames Basin, Libya. In both campaigns, complete fluid circulation loss was seen in these regions during up-hole drilling. Geophysics, sedimentology and shallow subsurface geology were all integrated to look into what was causing the seismic signal to disappear at shallow depths. The Upper Cretaceous Nalut Formation is the near-surface or surface formation in the studied area. It is distinguished by abnormally high resistivity in all the neighboring wells. The Nalut Formation in all the nearby wells from the present study and previous outcrop study suggests lithology of dolomite and chert/flint in nodular or layered forms. There are also reports of karstic caverns, vugs, and thick cracks, which all work together to produce the high resistivity. Four up-hole samples that were analyzed for microfacies revealed a near-coastal to tidal environment. Algal (Chara) infested deposits up to 30 feet thick and monotonous, very porous, are seen in two up-hole sediments; these deposits are interpreted to be scattered, continental algal travertine mounds. Chert/flint, dolomite, and calcite in varying amounts are confirmed by XRD analysis. Regional tracking of the high resistivity of the Nalut Formation, which is thought to be connected to the sea level drop that created the paleokarst layer, is possible. It is abruptly overlain by a blanket marine transgressive deposit caused by rapid sea level rise, which is a regional, relatively high radioactive layer of argillaceous limestone. The examined area's close proximity to the mountainous, E-W trending ridges of northern Libya made it easier for recent freshwater circulation, which later enhanced cavern development and mineralization in the paleokarst layer. Seismic signal loss at shallow depth is caused by extremely heterogeneous mineralogy of pore- filling or lack thereof. Scattering effect of shallow karstic layer on seismic signal has been well documented. Higher velocity inflection points at shallower depths in the northern part and deeper intervals in the southern part, in both cases at Nalut level, demonstrate the layer's influence on the seismic signal. During the Permian-Carboniferous, the Ghadames Basin underwent uplift and extensive erosion, which resulted in this karstic layer of the Nalut Formation uplifted to a shallow depth in the northern part of the studied area weakening the acoustic signal, whereas in the southern part of the 3D acquisition area the Nalut Formation remained at the deeper interval without affecting the seismic signal. Results from actions taken during seismic processing to deal with this signal loss are visible and have improved. This study recommends using denser spacing or dynamite to circumvent the karst layer in a comparable geographic area in order to prevent signal loss at lesser depths.

Keywords: well logging, seismic data acquisition, sesimic data processing, up-holes

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Authors: Georges F. Hatoum, Thomas H. Temple, Silvio Garcia, Xiaodong Wu

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Soft Tissue Sarcomas (STS) represent a diverse group of malignancies with heterogeneous clinical and pathological features. The treatment of extremity STS aims to achieve optimal local tumor control, improved survival, and preservation of limb function. The National Comprehensive Cancer Network guidelines, based on the cumulated clinical data, recommend radiation therapy (RT) in conjunction with limb-sparing surgery for large, high-grade STS measuring greater than 5 cm in size. Such treatment strategy can offer a cure for patients. However, when recurrence occurs (in nearly half of patients), the prognosis is poor, with a median survival of 12 to 15 months and with only palliative treatment options available. The spatially-fractionated-radiotherapy (SFRT), with a long history of treating bulky tumors as a non-mainstream technique, has gained new attention in recent years due to its unconventional therapeutic effects, such as bystander/abscopal effects. Combining single fraction of GRID, the original form of SFRT, with conventional RT was shown to have marginally increased the rate of pathological necrosis, which has been recognized to have a positive correlation to overall survival. In an effort to consistently increase the pathological necrosis rate over 90%, multiple fractions of Lattice RT (LRT), a newer form of 3D SFRT, interdigitated with the standard RT as neoadjuvant therapy was conducted in a preliminary clinical setting. With favorable results of over 95% of necrosis rate in a small cohort of patients, a Phase I/II clinical study was proposed to exam the safety and feasibility of this new strategy. Herein the design of the clinical study is presented. In this single-arm, two-stage phase I/II clinical trial, the primary objectives are >80% of the patients achieving >90% tumor necrosis and to evaluation the toxicity; the secondary objectives are to evaluate the local control, disease free survival and overall survival (OS), as well as the correlation between clinical response and the relevant biomarkers. The study plans to accrue patients over a span of two years. All patient will be treated with the new neoadjuvant RT regimen, in which one of every five fractions of conventional RT is replaced by a LRT fraction with vertices receiving dose ≥10Gy while keeping the tumor periphery at or close to 2 Gy per fraction. Surgical removal of the tumor is planned to occur 6 to 8 weeks following the completion of radiation therapy. The study will employ a Pocock-style early stopping boundary to ensure patient safety. The patients will be followed and monitored for a period of five years. Despite much effort, the rarity of the disease has resulted in limited novel therapeutic breakthroughs. Although a higher rate of treatment-induced tumor necrosis has been associated with improved OS, with the current techniques, only 20% of patients with large, high-grade tumors achieve a tumor necrosis rate exceeding 50%. If this new neoadjuvant strategy is proven effective, an appreciable improvement in clinical outcome without added toxicity can be anticipated. Due to the rarity of the disease, it is hoped that such study could be orchestrated in a multi-institutional setting.

Keywords: lattice RT, necrosis, SFRT, soft tissue sarcoma

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Authors: Nishanthi N. S., Srikanth Vedantam

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Intracellular delivery of materials has always proved to be a challenge in research and therapeutic applications. Usually, vector-based methods, such as liposomes and polymeric materials, and physical methods, such as electroporation and sonoporation have been used for introducing nucleic acids or proteins. Reliance on exogenous materials, toxicity, off-target effects was the short-comings of these methods. Microinjection was an alternative process which addressed the above drawbacks. However, its low throughput had hindered its adoption widely. Mechanical deformation of cells by squeezing them through constriction channel can cause the temporary development of pores that would facilitate non-targeted diffusion of materials. Advantages of this method include high efficiency in intracellular delivery, a wide choice of materials, improved viability and high throughput. This cell squeezing process can be studied deeper by employing simple models and efficient computational procedures. In our current work, we present a finite sized dissipative particle dynamics (FDPD) model to simulate the dynamics of the cell flowing through a constricted channel. The cell is modeled as a capsule with FDPD particles connected through a spring network to represent the membrane. The total energy of the capsule is associated with linear and radial springs in addition to constraint of the fixed area. By performing detailed simulations, we studied the strain on the membrane of the capsule for channels with varying constriction heights. The strain on the capsule membrane was found to be similar though the constriction heights vary. When strain on the membrane was correlated to the development of pores, we found higher porosity in capsule flowing in wider channel. This is due to localization of strain to a smaller region in the narrow constriction channel. But the residence time of the capsule increased as the channel constriction narrowed indicating that strain for an increased time will cause less cell viability.

Keywords: capsule, cell squeezing, dissipative particle dynamics, intracellular delivery, microfluidics, numerical simulations

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Authors: Daniela Proca, Yuan Rong, Salvatore Luceno, Jalil Nasibli

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Introduction: Solitary Fibrous Tumors (SFT) have many histologic mimickers and the only way to diagnose it, particularly in an unusual location, such as peripheral nerve trunks, is to use a comprehensive immunohistochemical staining panel. Monoclonal STAT6 immunostain is highly sensitive and specific for SFTs and particularly useful in the diagnosis of difficult SFT cases. Methods: We describe a solitary fibrous tumor (SFT) involving the right branchial plexus in a 66 yo female with 4-year history of slowly growing chest wall mass with recent dysesthesias in fingers 4th and 5th. MRI showed a well-circumscribed heterogenous mass measuring 5.4 x 3.8 x 4.0 cm and encircling peripheral nerves of the branchial plexus; no involvement of the bone or muscle was noted. A biopsy showed a bland spindled and epithelioid proliferation with no significant mitotic activity, no necrosis, and no atypia; peripheral nerve fascicles were encircled by the lesion. The main clinical and pathologic differential diagnosis included peripheral nerve sheath tumor, particularly schwannoma; HE microscopy didn’t show the classic Antoni A and B areas but showed focal subtle nuclear palisading, as well as prominent vessels with hyalinization. Immunohistochemical stains showed focal, weak cytoplasmic S100 positivity in the lesion; CD 34 and Vimentin were strongly and diffusely positive; the neoplastic cells were negative with AE1/AE3, EMA, CD31, SMA, Desmin, Calretinin, HMB-45, Melan A, PAX-8, NSE. The immunohistochemical and histologic pattern was not typical of peripheral nerve sheath tumor. On additional stains, the tumor was positive with STAT-6 and bcl-2 and focally positive with CD99. Given this profile, the final diagnosis was that of a solitary fibrous tumor. Results: NA Conclusion: Very few SFTs involving peripheral nerves and mimicking a peripheral nerve sheath tumor are described in the literature. Although histologically benign on this biopsy, long-term follow-up is required because of the risk of recurrence of these tumors and their uncertain biological behavior.

Keywords: solitary fibrous tumor, pathology, diagnosis, immunohistochemistry

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Authors: Elisabeth Louise Ndjengue Mindang, Charline Florence Awounfack, Derek Tantoh Ndinteh, Rui W. M. Krause, Dieudonne Njamen

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The evolution of human fertility over the last 50 years has shown considerable problems due to a growing number of couples that find it difficult to procreate without medical assistance. In Africa, this inability to conceive affect 30 to 40% of couples. A number of contaminants in the environment are thought to contribute significantly to the observed infertility epidemic. Methods: On this basis, the impact of 40-days unique oral administration (between 9 and 10 am) of potassium sorbate (at of 12.5, 45, and 78 mg/kg BW doses) was evaluated on sexual maturation and hematologic parameters on immature Wistar rats (21-22 days of age). At the end of the treatment, animals were sacrificed. Vaginal opening was evaluated before the sacrifice. After the sacrifice, relative weight of reproductive organs, pituitary gonadotrophin level (LH and FSH), and sexuals steroids (estrogen and progesterone), cholesterol level in ovaries, folliculogenesis, and some hematological parameters were evaluated. Results: Compared to the control group, no significant variation was observed in the body weight of the animals treated with patassium sorbate. On the other hand, potassium sorbate, a significantly lower percentage (25%) of vaginal-opening in these rats, was observed from day 46 of age (p <0.01); likewise, a significant decrease was observed on the relative weight of the ovaries (p <0.01), number of primary follicles (p <0.01), and a significant increase of follicle number (p <0.001) at 78 mg/kg BW have been obseved. Potassium sorbate always decreased the number of white blood cells (p <0.05). Taken together, these results confirm the disturbing effects on the endocrine system, causing a decrease in fertility by increasing the number of follicles in atresia. A deleterious effect on the immune system was also observed. Overall, these results validate at least in part the global observations on the growing decline in fertility in populationsfeeding increasingly on industrial processed foods.

Keywords: potassium sorbate, early puberty, folliculogenesis, endocrine disruptor, immatur wistar rat

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Authors: Zakia Hbellaq

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The Mediterranean region is considered a hotbed for climate change. Morocco is a semi-arid Mediterranean country facing water shortages and poor water quality. Its limited water resources limit the activities of various economic sectors. Most of Morocco's territory is in arid and desert areas. The potential water resources are estimated at 22 billion m3, which is equivalent to about 700 m3/inhabitant/year, and Morocco is in a state of structural water stress. Strictly speaking, the Kingdom of Morocco is one of the “very riskiest” countries, according to the World Resources Institute (WRI), which oversees the calculation of water stress risk in 167 countries. The surprising results of the Institute (WRI) rank Morocco as one of the riskiest countries in terms of water scarcity, ranking 3.89 out of 5, thus occupying the 23rd place out of a total of 167 countries, which indicates that the demand for water exceeds the available resources. Agriculture with a score of 3.89 is most affected by water stress from irrigation and places a heavy burden on the water table. Irrigation is an unavoidable technical need and has undeniable economic and social benefits given the available resources and climatic conditions. Irrigation, and therefore the agricultural sector, currently uses 86% of its water resources, while industry uses 5.5%. Although its development has undeniable economic and social benefits, it also contributes to the overfishing of most groundwater resources and the surprising decline in levels and deterioration of water quality in some aquifers. In this context, REUSE is one of the proposed solutions to reduce the water footprint of the agricultural sector and alleviate the shortage of water resources. Indeed, wastewater reuse, also known as REUSE (reuse of treated wastewater), is a step forward not only for the circular economy but also for the future, especially in the context of climate change. In particular, water reuse provides an alternative to existing water supplies and can be used to improve water security, sustainability, and resilience. However, given the introduction of organic trace pollutants or, organic micro-pollutants, the absorption of emerging contaminants, and decreasing salinity, it is possible to tackle innovative capabilities to overcome these problems and ensure food and health safety. To this end, attention will be paid to the adoption of an integrated and attractive approach, based on the reinforcement and optimization of the treatments proposed for the elimination of the organic load with particular attention to the elimination of emerging pollutants, to achieve this goal. , membrane bioreactors (MBR) as stand-alone technologies are not able to meet the requirements of WHO guidelines. They will be combined with heterogeneous Fenton processes using persulfate or hydrogen peroxide oxidants. Similarly, adsorption and filtration are applied as tertiary treatment In addition, the evaluation of crop performance in terms of yield, productivity, quality, and safety, through the optimization of Trichoderma sp strains that will be used to increase crop resistance to abiotic stresses, as well as the use of modern omics tools such as transcriptomic analysis using RNA sequencing and methylation to identify adaptive traits and associated genetic diversity that is tolerant/resistant/resilient to biotic and abiotic stresses. Hence, ensuring this approach will undoubtedly alleviate water scarcity and, likewise, increase the negative and harmful impact of wastewater irrigation on the condition of crops and the health of their consumers.

Keywords: water scarcity, food security, irrigation, agricultural water footprint, reuse, emerging contaminants

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