Search results for: host transcriptome and drug repurposing

Authors: Akhtar Aman, Abida Raza, Shumaila Bashir, Mehboob Alam

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The development of efficient delivery systems remains a major concern in cancer chemotherapy as many efficacious anticancer drugs are hydrophobic and difficult to formulate. Nanomedicines based on drug-loaded amphiphilic glycol chitosan micelles offer potential advantages for the formulation of drugs such as etoposide that may improve the pharmacokinetics and reduce the formulation-related adverse effects observed with current formulations. Amphiphilic derivatives of glycol chitosan were synthesized by chemical grafting of palmitic acid N-hydroxysuccinimide and quaternization to glycol chitosan backbone. To this end, a 7.9 kDa glycol chitosan was modified by palmitoylation and quaternization, yielding a 13 kDa amphiphilic polymer. Micelles prepared from this amphiphilic polymer had a size of 162nm and were able to encapsulate up to 3 mg/ml etoposide. Pharmacokinetic results indicated that the GCPQ micelles transformed the biodistribution pattern and increased etoposide concentration in the brain significantly compared to free drugs after intravenous administration. AUC 0.5-24h showed statistically significant difference in ETP-GCPQ vs. Commercial preparation in liver (25 vs.70, p<0.001), spleen (27 vs.36, p<0.05), lungs (42 vs.136,p<0.001),kidneys(25 vs.70,p< 0.05),and brain(19 vs.9,p<0.001). ETP-GCPQ crossed the blood-brain barrier, and 4, 3.5, 2.6, 1.8, 1.7, 1.5, and 2.5 fold higher levels of etoposide were observed at 0.5, 1, 2, 4, 6, 12, and 24hrs; respectively suggesting these systems could deliver hydrophobic anticancer drugs such as etoposide to tumors but also increased their transport through the biological barriers, thus making it a good delivery system

Keywords: glycol chitosan, micelles, pharmacokinetics, tissue distribution

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Authors: Carmen Nechita

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This research explores the world of Syrian refugee women living in Dresden and their efforts to reconstruct their lives in the state of Saxony in Germany. The focus is on the initial period of adjustment and understanding how refugee women use culture, family ties, and tradition to contest and rebuild new relationships with the host country. Faced with a new status as “the refugee”, women have to re-imagine their ethno-cultural identity in order to cope with life in Diaspora. In order to understand the coping mechanism and the displacement effects on Syrian women, interviews with twelve refugee women were conducted. Traumatic experiences of loss and oppression are at the core of their confessions. While gender violence, abuse and patriarchal framework shape their narratives, this research argues that there is a need to look at this from a cultural perspective and try to distance ourselves from the western paradigm. The way Syrian women refute and rebuild their national and ethno-cultural identity in order to negotiate for themselves new space within German borders is explored. Two discourses are bridged: one of multiculturalism and one of tradition in order to explain how Syrian women experience western notions of family, womanhood and spousal dynamics. The process is painful, traumatic and marked by feelings of low self-worth, but in the end, new codes emerge and these women come out more empowered. The paper includes the migration experience and explores the ways in which Syrian refugee women tend to tell their complex stories, and how they reconstruct their identity in a new territory while faced with a different culture that discriminates against them. During the research, four distinct phases in the acculturation period were identified: “the survival”, “the honeymoon period”, “the isolation period” and “the anger period”. Each phase is analyzed in order to understand what triggers them, how women migrate from one phase to another and what can be done to make the process easier. This paper contributes to the field of refugee studies by offering a thorough understanding of the initial phases of the acculturation process in the case of Syrian refugee women. The study examines the fleeing and settlement experience in order to understand the complex ways that refugee women cope with the traumatic experience of settlement in another country and in a different culture. *Almanya: The Arabic word for Germany.

Keywords: displacement, migration, refugee women, Syria

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Authors: Md. Shadab, Mariyam N. Nashid, Venkata Srikanth Meka, Thiagarajan Madheswaran

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Naringenin (NAR), is a naturally occurring plant flavonoid, found predominantly in citrus fruits, that possesses a wide range of pharmacological properties including anti-oxidant, anti-inflammatory behaviour, cholesterol-lowering and anticarcinogenic activities. However, despite the therapeutic potential of naringenin shown in a number of animal models, its clinical development has been hindered due to its low aqueous solubility, slow dissolution rate and inefficient transport across biological membranes resulting in low bioavailability. Naringenin nanosuspension were produced using stabilizers Tween® 80 by high pressure homogenization techniques. The nanosuspensions were characterized with regard to size (photon correlation spectroscopy (PCS), size distribution, charge (zeta potential measurements), morphology, short term physical stability, dissolution profile and antioxidant potential. A nanocrystal PCS size of about 500 nm was obtained after 20 homogenization cycles at 1500 bar. The short-term stability was assessed by storage of the nanosuspensions at 4 ◦C, room temperature and 40 ◦C. Result showed that naringenin nanosuspension was physically unstable due to large fluctuations in the particle size and zeta potential after 30 days. Naringenin nanosuspension demonstrated higher drug dissolution (97.90%) compared to naringenin powder (62.76%) after 120 minutes of testing. Naringenin nanosuspension showed increased antioxidant activity compared to naringenin powder with a percentage DPPH radical scavenging activity of 49.17% and 31.45% respectively at the lowest DPPH concentration.

Keywords: bioavailability, naringenin, nanosuspension, oral delivery

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Authors: Tefera Worku Mekonnen, Hiseh Chih Tsai

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Enhancement of drug efficacy is essential in cancer treatment. The immune stimulator ovalbumin (Ova)-coated citric acid (AC-)-stabilized iron oxide nanoparticles (AC-IO-Ova NPs) and enhanced permeability and retention (EPR) based tumor targeted 4.5 (4.5G) poly(amidoamine) dendrimer-cisplatin nanocomplex (4.5GDP-Cis-pt NC) were used for enhanced anticancer efficiency. The formations of 4.5GDP-Cis-pt NC, AC-IO, and AC-IO-Ova NPs have been examined by FTIR, X-ray diffraction, Raman, and X-ray photoelectron spectroscopy. The conjugation of cisplatin (Cis-pt) with 4.5GDP was confirmed using carbon NMR. The tumor-specific 4.5GDP-Cis-pt NC provided ~45% and 28% cumulative cisplatin release in 72 h at pH 6.5 and 7.4, respectively. A significant immune response with high TNF-α and IL-6 cytokine secretion was confirmed when the co-incubation of AC-IO-Ova with RAW 264.7 or HaCaT cells. AC-IO-Ova NP was biocompatible in different cell lines, even at a high concentration (200 µg mL−1). In contrast, AC-IO-Ova NPs mixed with 4.5GDP-Cis-pt NC (Cis-pt at 15 µg mL−1) significantly increased the cytotoxicity against the cancer cells, which is dose-dependent on the concentration of AC-IO-Ova NPs. The increased anticancer effects may be attributed to the generation of reactive oxygen species (ROS). Moreover, the efficiency of anticancer cells may be further assisted by induction of an innate immune response via M1 macrophage polarization due to the presence of AC-IO-Ova NPs. We provide a better synergestic chemoimmunotherapeutic strategy to enhance the efficiency of anticancer of cisplatin via chemotherapeutic agent 4.5GDP-Cis-pt NC and induction of proinflammatory cytokines to stimulate innate immunity through AC-IO-Ova NPs against tumors.

Keywords: cisplatin-release, iron oxide, ovalbumin, poly(amidoamine) dendrimer

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Authors: Jabulani Gilford Kheswa

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This paper reports on the effects of unemployment on the sexual behaviour of male youth. Drawing from Jahoda’s deprivation theory, unemployed male youth is prone to psychological distress and as a result, they resort to drugs and alcohol abuse as a way to cope with discrimination. Studies showed that such youth is more inclined to be sexually aggressive and very often engage in criminal activities and risky sexual behaviour such as multiple sexual partners and unprotected sex to cover their feelings of emotional insecurities and negative self-concept. The purpose of the study was to investigate the impact of unemployment on the sexual behaviour of Xhosa- speaking male youth, aged 19-35, from Quzini Location, Eastern Cape, South Africa. A qualitative, explorative, descriptive and contextual design was followed using phenomenological method. The purposively sampled comprised fifteen unemployed males who gave their informed consent to be interviewed. For trustworthiness of the study, the researcher met the Lincoln and Guba’s principles, namely; credibility, dependability confirmability and transferability. The following themes were identified, namely; patriarchy, gender- based violence, drug abuse, stigma and discrimination, criminal activities, depression and low- self-esteem. Based on the findings, the recommendations are that the government and private sectors should create jobs aimed at reducing unemployment for unemployed youth and psycho-educational programmes that will equip them in the areas of sexual values and attitudes, communication and decision-making skills.

Keywords: discrimination, male-youth, sex, unemployment

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Authors: Oluwatofunmi Musa-Ajakaiye, Paul Olorunfemi M.D MPH, John Obafaiye

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Introduction: The U.S Food and Drug Administration (FDA) reports the public notices for recalled FDA-regulated products over periods of time. It study reviewed the primary reasons for recalls of products of various types over a period of 7 years. Methods: The study analyzed data provided in the FDA’s archived recalls for the years 2010-2017. It identified the various reasons for product recalls in the categories of foods, beverages, drugs, medical devices, animal and veterinary products, and dietary supplements. Using SPSS version 29, descriptive statistics and chi-square analysis of the data were performed. Results (numbers, percentages, p-values, chi-square): Over the period of analysis, a total of 931 recalls were reported. The most frequent reason for recalls was undeclared products (36.7%). The analysis showed that the most recalled product type in the data set was foods and beverages, representing 591 of all recalled products (63.5%).In addition, it was observed that foods and beverages represent 77.2% of products recalled due to the presence of microorganisms. Also, a sub-group analysis of recall reasons of food and beverages found that the most prevalent reason for such recalls was undeclared products (50.1%) followed by Listeria (17.3%) then Salmonella (13.2%). Conclusion: This analysis shows that foods and beverages have the greatest percentages of total recalls due to the presence of undeclared products listeria contamination and Salmonella contamination. The prevalence of Salmonella and Listeria contamination suggests that there is a high risk of microbial contamination in FDA-approved products and further studies on the effects of such contamination must be conducted to ensure consumer safety.

Keywords: food, beverages, listeria, salmonella, FDA, contamination, microbial

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Authors: Mohd. A. M. Rahim, Yahaya Hassan, Mathumalar L. Fahrni

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Second line antiretroviral therapy (ART) regimen is used when patients fail their first line regimen. There are many factors such as non-adherence, drug resistance as well as virological and immunological failure that lead to second line highly active antiretroviral therapy (HAART) regimen treatment failure. This study was aimed at determining predictor factors to treatment failure with second line HAART and analyzing median survival time. An observational, retrospective study was conducted in Sungai Buloh Hospital (HSB) to assess current status of HIV patients treated with second line HAART regimen. Convenience sampling was used and 104 patients were included based on the study’s inclusion and exclusion criteria. Data was collected for six months i.e. from July until December 2013. Data was then analysed using SPSS version 18. Kaplan-Meier and Cox regression analyses were used to measure median survival times and predictor factors for treatment failure. The study population consisted mainly of male subjects, aged 30-45 years, who were heterosexual, and had HIV infection for less than 6 years. The most common second line HAART regimen given was lopinavir/ritonavir (LPV/r)-based combination. Kaplan-Meier analysis showed that patients on LPV/r demonstrated longer median survival times than patients on indinavir/ritonavir (IDV/r) based combination (p<0.001). The commonest reason for a treatment to fail with second line HAART was non-adherence. Based on Cox regression analysis, other predictor factors for treatment failure with second line HAART regimen were age and mode of HIV transmission.

Keywords: adherence, antiretroviral therapy, second line, treatment failure

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Authors: Celestine Mbakaan, Iorkyaa Ahemen, A. D. Onoja, A. N. Amah, Emmanuel Barki

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Rice husk (RH) is a natural sheath that forms and covers the grain of rice. The husk composed of hard materials, including opaline silica and lignin. It separates from its grain during rice milling. RH also contains approximately 15 to 28 wt % of silica in hydrated amorphous form. Nanosilica was derived from the husk of different rice varieties after pre-treating the husk (RH) with HCl and calcination at 550°C. Nanosilica derived from the husk of Osi rice variety produced the highest silica yield, and further pretreatment with 0.8 M H₃PO₄ acid removed more mineral impurities. The silica obtained from this rice variety was selected as a host matrix for doping with Sm³⁺ ions. Rice husk silica (RH-SiO₂) doped with samarium (RH-SiO₂: xSm³⁺ (x=0.01, 0.05, and 0.1 molar ratios) nanophosphors were synthesized via the sol-gel method. The structural analysis by X-ray diffraction analysis (XRD) reveals amorphous structure while the surface morphology, as revealed by SEM and TEM, indicates agglomerates of nano-sized spherical particles with an average particle size measuring 21 nm. The nanophosphor has a large surface area measuring 198.0 m²/g, and Fourier transform infrared spectroscopy (FT-IR) shows only a single absorption band which is strong and broad with a valley at 1063 cm⁻¹. Diffuse reflectance spectroscopy (DRS) shows strong absorptions at 319, 345, 362, 375, 401, and 474 nm, which can be exclusively assigned to the 6H5/2→4F11/2, 3H7/2, 4F9/2, 4D5/2, 4K11/2, and 4M15/2 + 4I11/2, transitions of Sm³⁺ respectively. The photoluminescence excitation spectra show that near UV and blue LEDs can effectively be used as excitation sources to produce red-orange and yellow-orange emission from Sm³⁺ ion-doped RH-SiO₂ nanophosphors. The photoluminescence (PL) of the nanophosphors gives three main lines; 568, 605, and 652 nm, which are attributed to the intra-4f shell transitions from the excited level to ground levels, respectively under excitation wavelengths of 365 and 400 nm. The result, as confirmed from the 1931 CIE coordinates diagram, indicates the emission of red-orange light by RH-SiO₂: xSm³⁺ (x=0.01 and 0.1 molar ratios) and yellow-orange light from RH-SiO₂: 0.05 Sm³⁺. Finally, the result shows that RH-SiO₂ doped with samarium (Sm³⁺) ions can be applicable in display applications.

Keywords: luminescence, nanosilica, nanophosphors, Sm³⁺

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Authors: Lien Gysens, Bert Vanmechelen, Maarten Haspeslagh, Piet Maes, Ann Martens

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Bovine papillomavirus (BPV) types 1 and 2 play a central role in the etiology of the most common neoplasm in horses, the equine sarcoid. The unknown mechanism behind the unique variety in a clinical presentation on the one hand and the host-dependent clinical outcome of BPV-1 infection, on the other hand, indicate the involvement of additional factors. Earlier studies have reported the potential functional significance of intratypic sequence variants, along with the existence of sarcoid-sourced BPV variants. Therefore, intratypic sequence variation seems to be an important emerging viral factor. This study aimed to give a broad insight in sarcoid-sourced BPV variation and explore its potential association with disease presentation. In order to do this, a nanopore sequencing approach was successfully optimized for screening a wide spectrum of clinical samples. Specimens of each tumour were initially screened for BPV-1/-2 by quantitative real-time PCR. A custom-designed primer set was used on BPV-positive samples to amplify the complete viral genome in two multiplex PCR reactions, resulting in a set of overlapping amplicons. For phylogenetic analysis, separate alignments were made of all available complete genome sequences for BPV-1/-2. The resulting alignments were used to infer Bayesian phylogenetic trees. We found substantial genetic variation among sarcoid-derived BPV-1, although this variation could not be linked to disease severity. Several of the BPV-1 genomes had multiple major deletions. Remarkably, the majority of the cluster within the region coding for late viral genes. Together with the extensiveness (up to 603 nucleotides) of the described deletions, this suggests an altered function of L1/L2 in disease pathogenesis. By generating a significant amount of complete-length BPV genomes, we succeeded in introducing next-generation sequencing into veterinary research focusing on the equine sarcoid, thus facilitating the first report of both nanopore-based sequencing of complete sarcoid-sourced BPV-1/-2 and the simultaneous nanopore sequencing of multiple complete genomes originating from a single clinical sample.

Keywords: Bovine papillomavirus, equine sarcoid, horse, nanopore sequencing, phylogenetic analysis

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Authors: Ahmad Lutfi, Nikolas Dhega

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The Malala deposit in northwest Sulawesi is the only known porphyry molybdenum and the only source for rhenium, occurrence in Indonesia. The neural network method produces results that correspond very closely to those of the knowledge-based fuzzy logic method and weights of evidence method. This method required data of solid geology, regional faults, airborne magnetic, gamma-ray survey data and GIS data. This interpretation of the network output fits with the intuitive notion that a prospective area has characteristics that closely resemble areas known to contain mineral deposits. Contrasts with the weights of evidence and fuzzy logic methods, where, for a given grid location, each input-parameter value automatically results in an increase in the prospective estimated. Malala District indicated molybdenum anomalies in stream sediments from in excess of 15 km2 were obtained, including the Takudan Fault as most prominent structure with striking 40̊ to 60̊ over a distance of about 30 km and in most places weakly at anomaly B, developed over an area of 4 km2, with a ‘shell’ up to 50 m thick at the intrusive contact with minor mineralization occurring in the Tinombo Formation. Series of NW trending, steeply dipping fracture zones, named the East Zone has an estimated resource of 100 Mt at 0.14% MoS2 and minimum target of 150 Mt 0.25%. The Malala porphyries occur as stocks and dykes with predominantly granitic, with fluorine-poor class of molybdenum deposits and belongs to the plutonic sub-type. Unidirectional solidification textures consisting of subparallel, crenulated layers of quartz that area separated by layers of intrusive material textures. The deuteric nature of the molybdenum mineralization and the dominance of carbonate alteration.The nature of the Stage I with alteration barren quartz K‐feldspar; and Stage II with alteration quartz‐K‐feldspar‐apatite-molybdenite veins combined with the presence of disseminated molybdenite with primary biotite in the host intrusive.

Keywords: molybdenite, Malala, porphyries, anomaly B

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Authors: Gehan F. Abdel Raoof, Ataa A. Said, Khaled Y. Mohamed, Hala M. Mohammed

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Pleiogynium timorense(DC.) Leenh is one of the therapeutically active plants belonging to the family Anacardiaceae. The bark of Pleiogynium timorense needs further studies to investigate its phytochemical and biological activities. This work was carried out to investigate the chemical composition of petroleum ether extract of Pleiogynium timorense bark as well as to evaluate the analgesic and anti-inflammatory activities. The unsaponifiable matter and fatty acid methyl esters were analyzed by Gas chromatography–mass spectrometry (GC-MS). Moreover, analgesic and anti-inflammatory activities were evaluated using acetic acid-induced writhing test and carrageen hind paw oedema models in rats, respectively. The results showed that twenty one compounds in the unsaponifiable fraction were identified representing 92.54 % of the total beak area, the major compounds were 1-Heptene (35.32%), Butylated hydroxy toluene (19.42%) and phytol (12.53%), whereas fifteen compounds were identified in the fatty acid methyl esters fraction representing 94.15% of the total identified peak area. The major compounds were 9-Octadecenoic acid methyl ester (35.34%) and 9,12-Octadecadienoic acid methyl ester (29.32%). Moreover, petroleum ether extract showed a significant reduction in pain and inflammation in a dose dependent manner. This study aims to be the first step toward the use of petroleum ether extract of Pleiogynium timorense bark as analgesic and anti-inflammatory drug.

Keywords: analgesic, anti-inflammatory, bark, petroleum ether extract, Pleiogynium timorense

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Authors: Muneeb Nasir, Misbah Masood, Farrukh Rashid, Abubabakar Shahid

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Introduction: Neo-adjuvant chemotherapy is a potent option for triple negative breast cancer (TNBC) as these tumours lack a clearly defined therapeutic target. Several recent studies lend support that pathological complete remission (pCR) is associated with improved disease free survival (DFS) and overall survival (OS) and could be used as surrogate marker for DFS and OS in breast cancer patients. Methods: We have used a four-drug protocol in T3 and T4 TNBC patients either N+ or N- in the neo-adjuvant setting. The 15 patients enrolled in this study had a median age of 45 years. 12 patients went on to complete four planned cycles of B-CAT protocol. The chemotherapy regimen included inj. Bevacizumab 5mg/kg D1, inj. Adriamycin 50mg/m2 D1 and Docetaxel 65mg/m2 on D1. Inj. Cisplatin 60mg/m2 on D2. All patients received GCF support from D4 to D9 of each cycle. Results: Radiological assessment using ultrasound and PET-CT revealed a high percentage of responses. Radiological CR was documented in half of the patients (6/12) after four cycles. Remaining patients went on to receive 2 more cycles before undergoing radical surgery. pCR was documented in 7/12 patients and 3 more had a good partial response. The regimen was toxic and grade ¾ neutropenia was seen in 58% of patients. Four episodes of febrile neutropenia were reported and managed. Non-hematatological toxicities were common with mucositis, diarrhea, asthenia and neuropathy topping the list. Conclusion: B-CAT is a very active combination with very high pCR rates in TNBC. Toxicities though frequent, were manageable on outpatient basis. This protocol warrants further investigation.

Keywords: B-CAT:bevacizumab, cisplatin, adriamycin, taxotere, CR: complete response, pCR: pathological complete response, TNBC: triple negative breast cancer

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Authors: Andreas Aceranti, Sergio Romanò, Simonetta Vernocchi, Silvia Arnaboldi, Emilio Mazza

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As a result of the Sars-Cov2 pandemic, the incidence of thymism disorders has significantly increased and, often, patients are reluctant to want to take drugs aimed at stabilizing mood. In order to provide an alternative approach to drug therapies, we have prepared a study in order to evaluate the possibility of improving the quality of life of these subjects through osteopathic treatment. Patients were divided into visceral and fascial manual treatment with the aim of increasing serotonin levels and stimulating the vagus nerve through validated techniques. The results were evaluated through the administration of targeted questionnaires in order to assess quality of life, mood, sleep and intestinal functioning. At a first endpoint we found, in patients undergoing fascial treatment, an increase in quality of life and sleep: in fact, they report a decrease in the number of nocturnal awakenings; a reduction in falling asleep times and greater rest upon waking. In contrast, patients undergoing visceral treatment, as well as those included in the control group, did not show significant improvements. Patients in the fascial group have, in fact, reported an improvement in thymism and subjective quality of life with a generalized improvement in function. Although the study is still ongoing, based on the results of the first endpoint we can hypothesize that fascial stimulation of the vagus nerve with manual and osteopathic techniques may be a valid alternative to pharmacological treatments in mood and sleep disorders.

Keywords: ostheopathy, insomnia, noctural awakening, thymism

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Authors: Arunima Verma, Padmabati Mondal

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Serotonin-receptor binding plays a key role in several neurological and biological processes, including mood, sleep, hunger, cognition, learning, and memory. In this article, we performed molecular dynamics simulation to examine the key residues that play an essential role in the binding of serotonin to the G-protein-coupled 5-HT₁ᴮ receptor (5-HT₁ᴮ R) via electrostatic interactions. An end-point free energy calculation method (MM-PBSA) determines the stability of the 5-HT1B R due to serotonin binding. The single-point mutation of the polar or charged amino acid residues (Asp129, Thr134) on the binding sites and the calculation of binding free energy validate the importance of these residues in the stability of the serotonin-receptor complex. Principal component analysis indicates the serotonin-bound 5-HT1BR is more stabilized than the apo-receptor in terms of dynamical changes. The difference dynamic cross-correlations map shows the correlation between the transmembrane and mini-Go, which indicates signal transduction happening between mini-Go and the receptor. Allosteric communication reveals the key nodes for signal transduction in 5-HT1BR. These results provide useful insights into the signal transduction pathways and mutagenesis study to regulate the functionality of the complex. The developed protocols can be applied to study local non-covalent interactions and long-range allosteric communications in any protein-ligand system for computer-aided drug design.

Keywords: allostery, CADD, MD simulations, MM-PBSA

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Authors: Surarong Chinwong, Namthip Intarakumhang Na Rachasima, Siyaporn Kuikhiew, Dujrudee Chinwong

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Irrational use of medicines is a major problem in public health. Half of all patients take medicines incorrectly. An inappropriate use of antibiotics is one of the common types of irrational medicine use; for example, patients use antibiotic for treatment of common cold or diarrhea. Objectives: This cross-sectional study aimed to investigate the behaviors on antibiotic use, using amoxicillin and norfloxacin as examples, as well as sources of received health information. Methods: An online self-administered questionnaire was used to collect data from participants in Thailand between September and December 2015. Participants were asked about their behaviors on antibiotic use. Data were analyzed using descriptive statistics. Results: Of all 405 participants, most were female (65.3 %), aged 18-30 years (49.4 %), undergraduate or lower (69.7%), and civil servant or state enterprises (31.7 %). We found inappropriate behaviors in use of amoxicillin or norfloxacin: 1) there were 201/400 participants (50.3%) taking amoxicillin right away in case of having a common cold, such as having sore throat, running nose, and cough; 2) there were 170/405 participants (42.0%) using amoxicillin for relieving inflammatory symptoms, e.g. muscle inflammation or osteoarthritis; 3) there were 71/398 participants (17.8%) using amoxicillin as a muscle relaxant; 4) there were 135/398 participants (33.9%) using norfloxacin for treating diarrhea. Sources of health information received by the participants were from the internet (78.5%), the radio and/or television (42.2%), advertising publishing (33.3 %), and word of mouth (30.1%). Conclusion: This study showed improper behaviors in antibiotic use especially amoxicillin and norfloxacin. Health care providers including pharmacists should raise the public awareness on dangers of inappropriate antibiotic use and promote the rational use of antibiotics.

Keywords: antibiotic use, amoxicillin, norfloxacin, rational drug use

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Authors: Atlal El-Assaad

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Viruses change with time through mutations and result in new variants that may persist or disappear. A Mutation refers to an actual change in the virus genetic sequence, and a variant is a viral genome that may contain one or more mutations. Critical mutations may cause the virus to be more transmissible, with high disease severity, and more vulnerable to diagnostics, therapeutics, and vaccines. Thus, variants carrying such mutations may increase the risk to human health and are considered variants of concern (VOC). Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) - the contagious in humans, positive-sense single-stranded RNA virus that caused coronavirus disease 2019 (COVID-19) - has been studied thoroughly, and several variants were revealed across the world with their corresponding mutations. SARS-CoV-2 has four structural proteins, known as the S (spike), E (envelope), M (membrane), and N (nucleocapsid) proteins, but prior study and vaccines development focused on genetic mutations in the S protein due to its vital role in allowing the virus to attach and fuse with the membrane of a host cell. Specifically, subunit S1 catalyzes attachment, whereas subunit S2 mediates fusion. In this perspective, we studied all charged amino acid mutations of the SARS-CoV-2 viral spike protein S1 when bound to Antibody CC12.1 in a crystal structure and assessed the effect of different mutations. We generated all missense mutants of SARS-CoV-2 protein amino acids (AAs) within the SARS-CoV-2:CC12.1 complex model. To generate the family of mutants in each complex, we mutated every charged amino acid with all other charged amino acids (Lysine (K), Arginine (R), Glutamic Acid (E), and Aspartic Acid (D)) and studied the new binding of the complex after each mutation. We applied Poisson-Boltzmann electrostatic calculations feeding into free energy calculations to determine the effect of each mutation on binding. After analyzing our data, we identified charged amino acids keys for binding. Furthermore, we validated those findings against published experimental genetic data. Our results are the first to propose in silico potential life-threatening mutations of SARS-CoV-2 beyond the present mutations found in the five common variants found worldwide.

Keywords: SARS-CoV-2, variant, ionic amino acid, protein-protein interactions, missense mutation, AESOP

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Authors: Tuba Kizilirmak

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Distinct properties of porous metamaterials have been largely processed for biomedicine requiring a three-dimensional (3D) porous structure engaged with fine mechanical features, biodegradation ability, and biocompatibility. Applications of metamaterials are (i) porous orthopedic and dental implants; (ii) in vitro cell culture of metamaterials and bone regeneration of metamaterials in vivo; (iii) macro-, micro, and nano-level porous metamaterials for sensors, diagnosis, and drug delivery. There are some specific properties to design metamaterials for tissue engineering. These are surface to volume ratio, pore size, and interconnection degrees are selected to control cell behavior and bone ingrowth. In this study, additive manufacturing technique selective laser melting will be used to print the scaffolds. Selective Laser Melting prints the 3D components according to designed 3D CAD models and manufactured materials, adding layers progressively by layer. This study aims to design metamaterials with Ti6Al4V material, which gives benefit in respect of mechanical and biological properties. Ti6Al4V scaffolds will support cell attachment by conferring a suitable area for cell adhesion. This study will control the osteoblast cell attachment on Ti6Al4V scaffolds after the determination of optimum stiffness and other mechanical properties which are close to mechanical properties of bone. Before we produce the samples, we will use a modeling technique to simulate the mechanical behavior of samples. These samples include different lattice models with varying amounts of porosity and density.

Keywords: additive manufacturing, titanium lattices, metamaterials, porous metals

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Authors: Mallikarjunachari Gangapuram

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The design of stimuli-responsive hydrogel nanocomposite thin films is gaining significant attention in these days due to its wide variety of applications. Soft microrobots, drug delivery, biosensors, regenerative medicine, bacterial adhesion, energy storage and wound dressing are few advanced applications in different fields. In this research work, the nanomechanical properties of composite thin films of 20 microns were tuned by applying homogeneous external DC, and AC magnetic fields of magnitudes 0.05 T and 0.1 T. Polyvinyl alcohol (PVA) used as a matrix material and elliptical hematite nanoparticles (ratio of the length of the major axis to the length of the minor axis is 140.59 ± 1.072 nm/52.84 ± 1.072 nm) used as filler materials to prepare the nanocomposite thin films. Both quasi-static nanoindentation, Nano Dynamic Mechanical Analysis (Nano-DMA) tests were performed to characterize the viscoelastic properties of PVA, PVA+Hematite (0.1% wt, 2% wt and 4% wt) nanocomposites. Different properties such as storage modulus, loss modulus, hardness, and Er/H were carefully analyzed. The increase in storage modulus, hardness, Er/H and a decrease in loss modulus were observed with increasing concentration and DC magnetic field followed by AC magnetic field. Contact angle and ATR-FTIR experiments were conducted to understand the molecular mechanisms such as hydrogen bond formation, crosslinking density, and particle-particle interactions. This systematic study is helpful in design and modeling of magnetic responsive hydrogel nanocomposite thin films for biomedical applications.

Keywords: hematite, hydrogel, nanoindentation, nano-DMA

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Authors: Y. V. S. Annapurna, V. V. Lakshmi

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Urinary tract infection (UTI) is one of the most common infectious diseases at the community level with a high rate of morbidity . This is further augmented by increase in the number of resistant and multi resistant strains of bacteria particularly by those producing Extended spectrum of beta lactamases. The present study was aimed at analysis of antibiograms of E.coli and Klebsiella sp causing urinary tract infections. Between November 2011 and April 2013, a total of 1120 urine samples were analyzed,. Antibiotic sensitivity testing was done with 542(48%) isolates of E.coli and 446(39%) of Klebsiella sp using the standard disc diffusion method against eleven commonly used antibiotics .Organisms showed high susceptibility to Amikacin and Netilimicin and low susceptibility to Cephalosporins. MAR index was calculated for the multidrug resistant strains. Maximum MAR index detected among the isolates was 0.9. Phenotypic identification for ESBL production was confirmed by double disk synergy test (DDST) according to CLSI guidelines. Plasmid profile of the isolates was carried out using alkaline hydrolysis method. Agarose-gel electrophoresis showed presence of high-molecular weight plasmid DNA among the ESBL strains. This study emphasizes the importance of indiscriminate use of antibiotics which if discontinued, in turn would prevent further development of bacterial drug resistance. For this, a proper knowledge of susceptibility pattern of uropathogens is necessary before prescribing empirical antibiotic therapy and it should be made mandatory.

Keywords: escherichia coli, extended spectrum of beta lactamase, Klebsiella spp, Uropathogens

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Authors: Alok Pal Jain, Santram Lodhi

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Martynia annua Linn. (Martyniaccae) is traditionally used in inflammation and applied locally to tuberculosis glands of camel’s neck. The leaves used topically to bites of venomous insects and wounds of domestic animals. Chemical examination of Martynia annua leaves revealed the presence of glycosides, tannins, proteins, phenols and flavonoids. The present study was aimed to evaluate the anti-arthritic activity of methanolic extract of Martynia annua leaves. Methanolic extract of Martynia annua leaves was tested by using in vivo collagen-induced arthritis mouse model to investigate the anti-rheumatoid arthritis activity. In addition, antioxidant effect of methanolic extract was determined by the estimation of antioxidants level in joint tissues. The severity of arthritis was assessed by arthritis score and edema. Levels of cytokines TNF-α and IL-6, in the joint tissue homogenate were measured using ELISA. A high dose (250 mg/kg) of methanolic extract was significantly reduced the degree of inflammation in mice as compared with reference drug. Antioxidants level and malondialdehyde (MDA) in joint tissue homogenate found significantly (p < 0.05) higher. Methanolic extract at dose of 250 mg/kg modulated the cytokines production and suppressed the oxidative stress in the mice with collagen-induced arthritis. This study suggested that Martynia annua might be alternative herbal medicine for the management of rheumatoid arthritis.

Keywords: Martynia annua, collagen, rheumatoid arthritis, antioxidants

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Authors: S. A. Nirmal, J. M. Ingale, G. S. Asane, S. C. Pal, Subhash C. Mandal

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The present work was undertaken to determine the effects of Amaranthus roxburghianus Nevski. (Amaranthaceae) root alone and in combination with piperine in treating ulcerative colitis (UC) in mice. Swiss albino mice were divided into seven groups (n = 6). Standard group received prednisolone (5 mg/kg, i.p.). Treatment groups received hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and a combination of hydroalcoholic extract of roots of A. roxburghianus (50 and 100 mg/kg, p.o.) and piperine (5 mg/kg, p.o.). Ulcer index, colitis severity, myeloperoxidase (MPO), malondialdehyde and glutathione were estimated from blood and tissue. Column chromatography of the extract was done and purified fractions were analyzed by gas chromatography-mass spectroscopy (GC-MS). Treatment with the combination of hydroalcoholic extract of A. roxburghianus and piperine showed minimal ulceration, hemorrhage, necrosis and leucocyte infiltration by histopathological observation. Acetic acid increased MPO levels in blood and colon tissue to 355 U/mL and 385 U/mg, respectively. The combination of hydroalcoholic extract (100 mg/kg) and piperine (5 mg/kg) significantly decreased MPO in blood and tissue to 182 U/mL and 193 U/mg, respectively. Similarly, this combination significantly reduced MPO and increased glutathione levels in blood and tissue. Various phytoconstituents were detected by GC-MS. The combination of hydroalcoholic extract and piperine is effective in the treatment of UC and the effects are comparable with the standard drug prednisolone. 4H-pyran-4-one, 2,3-dihydro-3,5-dihydroxy-6-methyl, eugenol and benzene, and 1-(1,5-dimethyl-4-hexenyl)-4-methyl are reported having analgesic, anti-inflammatory, and antioxidant properties; they may play a role in the biological activity of A. roxburghianus root.

Keywords: Amaranthus roxburghianus, ulcerative colitis, anti-inflammatory, ulcerative colitis

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Authors: Iddrisu Ibrahim, Joseph Atia Ayariga, Junhuan Xu, Daniel Abugri, Boakai Robertson, Olufemi S. Ajayi

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The emergence of multidrug resistance poses a huge risk to public health globally. Yet these recalcitrant pathogens continue to rise in incidence rate, with resistance rates significantly outpacing the speed of antibiotic development. This, therefore, presents an aura of related health issues such as untreatable nosocomial infections arising from organ transplants and surgeries, as well as community-acquired infections that are related to people with compromised immunity, e.g., diabetic and HIV patients, etc. There is a global effort to fight multidrug-resistant pathogens spearheaded by the World Health Organization, thus calling for research into novel antimicrobial agents to fight multiple drug resistance. Previously, our laboratory demonstrated that Cannabidiol (CBD) was an effective antimicrobial against Salmonella typhimurium (S. typhimurium). However, we observed resistance development over time. To understand the mechanisms S. typhimurium uses to develop resistance to Cannabidiol (CBD), we studied the abundance of bacteria lipopolysaccharide (LPS) and membrane sterols of both susceptible and resistant S. typhimurium. Using real-time quantitative polymerase chain reaction (RT-qPCR), we also analyzed the expression of selected genes known for aiding resistance development in S. typhimurium. We discovered that there was a significantly higher expression of blaTEM, fimA, fimZ, and integrons in the CBD-resistant bacteria, and these were also accompanied by a shift in abundance in cell surface molecules such as lipopolysaccharide (LPS) and sterols.

Keywords: antimicrobials, resistance, cannabidiol, gram-negative bacteria, integrons, blaTEM, Fim, LPS, ergosterols

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Authors: Mukesh Lal Das, Muthukumar Muthuchamy

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Climate change Adaptation strategy (AS) is a scientific approach to dealing with the impacts of climate change (CC). Efforts are being made to contain the global emission of greenhouse gas within threshold limits, thereby limiting the rise of global temperature to an optimal level. Global Climate change is a spontaneous process; therefore, reversing the damage would take decades. The climate change adaptation strategy recommended by various stakeholders could be a key to resilience for biodiversity. The Indian Government has constituted the panel to synthesize the climate change action report at the federal and state levels. This review scavenged the published literature on the Western Ghats hotspots. And highlight the adaptation strategy recommended by diverse scientific actors to conserve biodiversity. It also reviews the grey literature adopted by state and federal governments and its effectiveness in mitigating the impacts on biodiversity. We have narrowed the scope of interest to the state action report by 6 Indian states such as Gujarat, Maharashtra, Goa, Karnataka, Kerala and Tamil Nadu, which host Western Ghats global biodiversity hotspot. Western Ghats(WGs) act as the water tower to the peninsular part of India, and its extensive watershed caters to the water demand of the Industry sector, Agriculture and urban community. Conservation of WGs is the key to the prosperity of Peninsular India. The global scientific community suggested more than 600+ Climate change adaptation strategies for the policymakers, stakeholders, and other state actors to take proactive actions. The preliminary analysis of the federal and the state action plan on climate change in the wake of CC indicate inadequacy in motion as per recommended scientific adaptation strategies. Tamil Nadu and Kerala state constitute nine effective adaptation strategies out of the 40+ recommended for Western Ghats conservation. And other four states' adaptation strategies are deficient, confusing and vague. Western Ghats' resilience capacity will soon or might have reached its threshold, and the frequency of severe drought and flash floods might upsurge manifold in the decades to come. The lack of a clear roadmap to climate change adaptation strategies in the federal and state action stirred us to identify the gap and address it by offering a holistic approach to WGs biodiversity conservation.

Keywords: adaptation strategy, biodiversity conservation, climate change, resilience, Western Ghats

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Authors: Emre Bayamlıoğlu

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This paper aims to provide an account of the legal and the regulative aspects of the algorithmic reputation systems with a special emphasis on the sharing economy (i.e., Uber, Airbnb, Lyft) business model. The first section starts with an analysis of the legal and commercial nature of the tripartite relationship among the parties, namely, the host platform, individual sharers/service providers and the consumers/users. The section further examines to what extent an algorithmic system of reputational information could serve as an alternative to legal regulation. Shortcomings are explained and analyzed with specific examples from Airbnb Platform which is a pioneering success in the sharing economy. The following section focuses on the issue of governance and control of the reputational information. The section first analyzes the legal consequences of algorithmic filtering systems to detect undesired comments and how a delicate balance could be struck between the competing interests such as freedom of speech, privacy and the integrity of the commercial reputation. The third section deals with the problem of manipulation by users. Indeed many sharing economy businesses employ certain techniques of data mining and natural language processing to verify consistency of the feedback. Software agents referred as "bots" are employed by the users to "produce" fake reputation values. Such automated techniques are deceptive with significant negative effects for undermining the trust upon which the reputational system is built. The third section is devoted to explore the concerns with regard to data mobility, data ownership, and the privacy. Reputational information provided by the consumers in the form of textual comment may be regarded as a writing which is eligible to copyright protection. Algorithmic reputational systems also contain personal data pertaining both the individual entrepreneurs and the consumers. The final section starts with an overview of the notion of reputation as a communitarian and collective form of referential trust and further provides an evaluation of the above legal arguments from the perspective of public interest in the integrity of reputational information. The paper concludes with certain guidelines and design principles for algorithmic reputation systems, to address the above raised legal implications.

Keywords: sharing economy, design principles of algorithmic regulation, reputational systems, personal data protection, privacy

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Authors: S. Fröhlich, M. Herold, M. Allmer

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Early stage quantitative analysis of host cell protein (HCP) variations is challenging yet necessary for comprehensive bioprocess development. High resolution mass spectrometry (HRMS) provides a high-end technology for accurate identification alongside with quantitative information. Hereby we describe a flexible HRMS assay platform to quantify HCPs relevant in microbial expression systems such as E. Coli in both up and downstream development by means of MVDA tools. Cell pellets were lysed and proteins extracted, purified samples not further treated before applying the SMART tryptic digest kit. Peptides separation was optimized using an RP-UHPLC separation platform. HRMS-MSMS analysis was conducted on an Orbitrap Velos Elite applying CID. Quantification was performed label-free taking into account ionization properties and physicochemical peptide similarities. Results were analyzed using SIEVE 2.0 (Thermo Fisher Scientific) and SIMCA (Umetrics AG). The developed HRMS platform was applied to an E. Coli expression set with varying productivity and the corresponding downstream process. Selected HCPs were successfully quantified within the fmol range. Analysing HCP networks based on pattern analysis facilitated low level quantification and enhanced validity. This approach is of high relevance for high-throughput screening experiments during upstream development, e.g. for titer determination, dynamic HCP network analysis or product characterization. Considering the downstream purification process, physicochemical clustering of identified HCPs is of relevance to adjust buffer conditions accordingly. However, the technology provides an innovative approach for label-free MS based quantification relying on statistical pattern analysis and comparison. Absolute quantification based on physicochemical properties and peptide similarity score provides a technological approach without the need of sophisticated sample preparation strategies and is therefore proven to be straightforward, sensitive and highly reproducible in terms of product characterization.

Keywords: process analytical technology, mass spectrometry, process characterization, MVDA, pattern recognition

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Authors: Abdulrazak Jinadu Otaru, Ahmed Almulhim, Hassan Alhassan, Mohammed Sabri

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Saudi Arabia is host to a state-owned oil and gas corporation, known as Saudi ARAMCO, that is responsible for the highest emissions of carbon dioxide (CO₂) due to the heavy reliance on fossil fuels as an energy source for various sectors such as transportation, aerospace, manufacturing, and residential use. Unfortunately, the detrimental consequences of CO₂ emissions include escalating temperatures in the Middle East region, posing significant obstacles in terms of food security and water scarcity for the Kingdom of Saudi Arabia. As part of the Saudi Vision 2030 initiative, which aims to reduce the country's reliance on fossil fuels by 50 %, this study focuses on designing a plant that will produce approximately 100,000 metric tons per year (MTPY) of green hydrogen (H₂) using brine as the primary feedstock. The proposed facility incorporates a double electrolytic technology that first separates brine or sodium chloride (NaCl) into sodium hydroxide, hydrogen gas, and chlorine gas. The sodium hydroxide is then used as an electrolyte in the splitting of water molecules through the supply of electrical energy in a second-stage electrolyser to produce green hydrogen. The study encompasses a comprehensive analysis of process descriptions and flow diagrams, as well as materials and energy balances. It also includes equipment design and specification, cost analysis, and considerations for safety and environmental impact. The design capitalizes on the abundant brine supply, a byproduct of the world's largest desalination plant located in Al Jubail, Saudi Arabia. Additionally, the design incorporates the use of available renewable energy sources, such as solar and wind power, to power the proposed plant. This approach not only helps reduce carbon emissions but also aligns with Saudi Arabia's energy transition policy. Furthermore, it supports the United Nations Sustainable Development Goals on Sustainable Cities and Communities (Goal 11) and Climate Action (Goal 13), benefiting not only Saudi Arabia but also other countries in the Middle East.

Keywords: plant design, electrolysis, brine, sodium hydroxide, chlorine gas, green hydrogen

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Authors: Giulia Balestracci

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Pakistan is endowed with diversified natural capital spanning along the 1000-kilometer-long coastline, shared by the coastal provinces of Sindh and Balochistan. It includes some of the most diverse, extensive, and least disturbed reef areas in the Indian Ocean. Pakistani marine and coastal ecosystems are fundamental for the social and economic well-being of the region. They support economic activities such as fishing, shrimp farming, tourism, and shipping, which contribute to income, food security, and the livelihood of millions of people. The coastal regions of Sindh and Balochistan are rich in natural resources and diverse ecosystems, and host also rural coastal communities that have been the keepers of rich cultural legacies and pristine natural landscapes. However, significant barriers hinder tourism development, such as the daunting socio-economic challenges, including the post-COVID-19 scenario, forced migration, institutional gaps, and the ravages of climate change. Pakistan holds immense potential for the tourism sector development within the framework of a sustainable blue economy, thereby fostering greener economic growth and employment opportunities, securing financing for the protection and conservation of its coastal and marine natural assets. Based on the assessment of Pakistan’s natural and cultural coastal and maritime tourism resources, a deep study of the regulatory and institutional aspects of the tourism sector in the country accompanied by the SWOT analysis and accompanied by an in-depth interview with a member of the Pakistan National Tourism Coordination Board (NTCB). A market analysis has been developed, and Lao PDR, Thailand, and Indonesia’s ecotourism development have been analyzed under a comparative analysis length to recommend some nature-based tourism activities for the sustainable development of the coastal areas in Pakistan. Nature-based tourism represents a win-win option as it uses economic incentives for the protection and cultural uses of natural resources. This article stresses the importance of nature-based activities for blue tourism, aligning conservation with developmental goals to safeguard natural resources and cultural heritage, all while fostering economic prosperity.

Keywords: blue tourism, coastal Pakistan, nature-based tourism, sustainable blue economy, sustainable development

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Authors: Heba Hozyen, Ragab Mohamed, Amal Abd El Hameed, Amal Abo El-Maaty

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This study aimed to investigate the effect of CIDR and ovsynch (Gonadotropin-prostaglandine-gonadotropin GPG) protocols for synchronization of follicular waves of dromedary camels on ovarian hormones, oxidative stress and conception during breeding season. Twelve dark colored dromedary camels were divided into two equal groups. The first group was subjected to CIDR insertion for 7 days and blood samples were collected each other day from the day of CIDR insertion (day 0) till day 21. The other group was subjected to GPG system (Ovsynch) and blood samples were collected daily for 11 days. Progesterone (P4) and estradiol were assayed using commercial ELISA diagnostic EIA kits. Catalase (CAT), total antioxidants capacity (TAC), glutathione reduced (GHD), lipid peroxide product (malondialdehyde, MDA) and nitric oxide (NO) were measured colorimetrically using spectrophotometer. Results revealed that CIDR treated camels had significantly high P4 (P= 0.0001), estradiol (P= 0.0001), CAT (P= 0.034), NO (P= 0.016) and TAC (P= 0.04) but significantly low MDA (P= 0.001) and GHD (P= 0.003) compared to GPG treated ones. Camels inserted with CIDR had higher conception rate (66.7%) compared to those treated with GPG (33%). In conclusion, camels treated with CIDR had higher hormonal response and antioxidant capacity than those synchronized with GPG which positively reflected on their conception rate. The better response of camels to CIDR and the higher conception compared to GPG protocol recommends its use for future reproductive management in camels.

Keywords: antioxidants, camel, CIDR, season, steroid hormones

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Authors: Don Anushka Sandaruwan Elvitigala, P. D. S. U. Wickramasinghe, Jehee Lee

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Cystatins are a large superfamily of proteins which act as reversible inhibitors of cysteine proteases. Papain proteases and cysteine cathepsins are predominant substrates of cystatins. Cystatin superfamily can be further clustered into three groups as Stefins, Cystatins, and Kininogens. Among them, stefines are also known as family 1 cystatins which harbors cystatin Bs and cystatin As. In this study, a homologue of family one cystatins more close to cystatin Bs was identified from Korean black rockfish (Sebastes schlegeli) using a prior constructed cDNA (complementary deoxyribonucleic acid) database and designated as RfCyt1. The full-length cDNA of RfCyt1 consisted of 573 bp, with a coding region of 294 bp. It comprised a 5´-untranslated region (UTR) of 55 bp, and 3´-UTR of 263 bp. The coding sequence encodes a polypeptide consisting of 97 amino acids with a predicted molecular weight of 11kDa and theoretical isoelectric point of 6.3. The RfCyt1 shared homology with other teleosts and vertebrate species and consisted conserved features of cystatin family signature including single cystatin-like domain, cysteine protease inhibitory signature of pentapeptide (QXVXG) consensus sequence and N-terminal two conserved neighboring glycine (⁸GG⁹) residues. As expected, phylogenetic reconstruction developed using the neighbor-joining method showed that RfCyt1 is clustered with the cystatin family 1 members, in which more closely with its teleostan orthologues. An SYBR Green qPCR (quantitative polymerase chain reaction) assay was performed to quantify the RfCytB transcripts in different tissues in healthy and immune stimulated fish. RfCyt1 was ubiquitously expressed in all tissue types of healthy animals with gill and spleen being the highest. Temporal expression of RfCyt1 displayed significant up-regulation upon infection with Aeromonas salmonicida. Recombinantly expressed RfCyt1 showed concentration-dependent papain inhibitory activity. Collectively these findings evidence for detectable protease inhibitory and immunity relevant roles of RfCyt1 in Sebastes schlegeli.

Keywords: Sebastes schlegeli, family 1 cystatin, immune stimulation, expressional modulation

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Authors: Nesrine Benarous, Hassiba Bougueria, Nabila Moussa Slimane, Aouatef Cherouana

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Crystal polymorphism is important for the synthesis of more potent and bioactive pharmaceutical compounds, including their different properties, such as packing arrangement and conformation. In fact, polymorphism plays a vital role in drug development. Different parameters affect the crystallization and give their degree of freedom. Severalproperties affected polymorphism, like kinetics, thermodynamics, spectroscopy, and mechanical property. Various techniques are used for characterizing polymorphs, are crystallography, morphology, phase transitions, molecular motion, and chemical environment. In this work, crystal structures of two polymorphs (I and II) of the Schiff base (SB) title compound were prepared by condensation reaction. The crystal structures of both polymorphs were determined by single X-ray analysis. The two polymorphs crystallize in two different space groups: P21/c for I and Pbca for II. The dihedral angles between the two phenyl rings are 4.81º for I and 82.27º for II. Both crystal structures are built on the basis of moderate and weak hydrogen bonds, 𝜋-stacking, and halogen⋯halogeninteractions. On the other hand, Hirshfeld surface (HS) analysis indicates that the most important contributions to the crystal packing for the two polymorphs are from Cl⋯H/H⋯Cl, H⋯H, and N⋯H/H⋯N contacts. These are followed by C⋯H/H⋯C for compound I and C⋯C and by C⋯H/H⋯C contacts for compound II. Afterwards, the in vitro antibacterial activity revealed that the SB have been found effective against G- bacteria Klebsiella pneumonia andG+ bacteria Staphylococcus aureuswith MIC value of14.37μg/mL. Moreover, the SBexhibited moderate toxicity against Brine Shrimp with LC50 value of 44.19μg/mL.

Keywords: polymorph, crystal structure, hirshfeld surface analysis, in vitro antibacterial activity, toxicity

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