Search results for: chronic inflammatory diseases

Authors: Latife Merve Oktay, Berrin Tugrul

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Hydroxytyrosol (HT) is a phenolic phytochemical molecule derived from the hydrolysis of oleuropein, which originates during the maturation of the olives. It has recently received particular attention because of its antioxidant, anti-proliferative, pro-apoptotic and anti-inflammatory activities. In this study, we investigated the cytotoxic and apoptotic effects of hydroxytyrosol and its effects on phosphatidylinositol 3-kinase/Akt (PI3K/Akt) and extracellular signal-regulated kinase 1/2 (ERK 1/2) signaling pathways in human ovarian cancer cell lines OVCAR-3 and MDAH-2774. XTT cell proliferation kit, Cell Death Detection Elisa Plus Kit (Roche) and Human Apoptosis Array (R&D Systems) were used to determine the cytotoxic and apoptotic effects of HT in OVCAR-3 and MDAH-2774 cell lines at 24, 48, 72, and 96 h. Effect of HT on PI3K/Akt and ERK 1/2 signaling pathways were investigated by using specific inhibitors of these pathways. IC50 values of HT were found to be 102.3 µM in MDAH-2774 cells at 72 h and 51.5 µM in OVCAR-3 cells at 96 h. Apoptotic effect of HT in MDAH-2774 cells was the highest at 50 µM at 72 h, and kept decreasing at 100 and 150 µM concentrations and was not seen at 200 µM and higher concentrations. Highest apoptotic effect was seen at 100 µM concentration in OVCAR-3 cells at 96 h, however apoptotic effect was decreased over 100 µM concentrations. According to antibody microarray results, HT increased the levels of pro-apoptotic molecules Bad, Bax, active caspase-3, Htra2/Omi by 2.0-, 1.4-, 1.2-, 4.2-fold, respectively and also increased the levels of pro-apoptotic death receptors TRAIL R1/DR4, TRAIL R2/DR5, FAS/TNFRSF6 by 2.1-, 1.7-, 1.6-fold, respectively, however, it decreased the level of Survivin by 1.6-fold which is one of the inhibitor of apoptosis protein (IAP) family in MDAH-2774 cells. In OVCAR-3 cells, HT decreased the levels of anti-apoptotic proteins Bcl-2, pro-caspase 3 by 3.1-, 8.2-fold, respectively and IAP family proteins CIAP-1, CIAP-2, XIAP, Livin, Survivin by 6.5-, 6.0-, 3.2-, 2.2-, 2.7-fold, respectively and increased the level of cytochrome-c by 1.2-fold. We have shown that HT shows its cytotoxic and apoptotic effect through inhibiting ERK 1/2 signaling pathway in both OVCAR-3 and MDAH-2774 cells. Further studies are needed to investigate molecular mechanisms and modulatory effects of hydroxytyrosol.

Keywords: apoptosis, cytotoxicity, hydroxytyrosol, ovarian cancer

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Authors: Eryati Darwin, Arina Widya Murni, Adnil Edwin Nurdin

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Background: Functional dyspepsia (FD) is a highly prevalent and heterogeneous disorder. Most patients with FD complain of symptoms related to the intake of meals. Psychological stress may promote peptic ulcer and had an effect on ulcers associated Hp, and may also trigger worsen symptoms in inflammatory disorders of the gastrointestinal. Cells in mucosal gastric stimulate the production of several cytokines, which might associated with Helicobacter pylori infection. The cascade of biological events leading to stress-induced FD remains poorly understood. Aim of Study: To determine the prion-flammatory cytokine IL-6, and Helicobacter pylori activity on mucosal gastric of FD and their association with psychological stress. Methods: The subjects of this study were dyspeptic patients who visited M. Djamil General Hospital and in two Community Health Centers in Padang. On the basis of the stress index scale to identify psychological stress by using Depression Anxiety and Stress Scale (DASS 42), subjects were divided into two groups of 20 each, stress groups and non-stress groups. All diagnoses were confirmed by review of cortisol and esophagogastroduodenoscopy reports. Gastric biopsy samples and peripheral blood were taken during diagnostic procedures. Immunohistochemistry methods were used to determine the expression of IL-6 and Hp in gastric mucosal. The data were statistically analyzed by univariate and bivariate analysis. All procedures of this study were approved by Research Ethics Committee of Medical Faculty Andalas University. Results: In this study, we enrolled 40 FD patients (26 woman and 14 men) in range between 35-56 years old. Cortisol level of blood FD patients as parameter of stress hormone which taken in the morning was significantly higher in stress group than non-stress group. The expression of IL-6 in gastric mucosa was significantly higher in stress group in compared to non-stress group (p<0,05). Helicobacter pylori activity in gastric mucosal in stress group were significantly higher than non-stress group. Conclusion: The present study showed that psychological stress can induce gastric mucosal inflammation and increase of Helicobacter pylori activity.

Keywords: functional dyspepsia, Helicobacter pylori, interleukin-6, psychological stress

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Authors: Muhammad Al Rizqi Dharma Fauzi, Dwi Yulian Fahruddin Shah, Andre Pratama, Ari Hasna Widyapuspa, Ganden Supriyanto

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Diabetes mellitus is still known as one of diseases which give a big amount of death in the world. From 2012 to 2014, diabetes is estimated to have resulted in 1.5 to 4.9 million deaths each year. In this paper, we present our research in the analysis and dose determination of Tenebrio molitor (Mealworm) extract as an anti-diabetic agent which is believed by Indonesian people as a traditional treatment to prevent and treat diabetes. We found that Tenebrio molitor extract has a potential as an anti-diabetic agent by in vitro test to Mus musculus which were divided into six group of treatment. Our dose determination analysis gave a conclusion that at 2,5 g/mL of concentration of the extract would give the optimal result in healing a wound given to Mus musculus which were induced by aloxane monohydrate. These results show that Tenebrio molitor extract is potential to be used as an Anti-Diabetic agent.

Keywords: diabetes, extraction, Tenebrio molitor, traditional medicine

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Authors: Zatovska T. V., Nesterova N. V., Baranova G. V., Zagorodnya S. D.

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In recent years, biosensor technologies based on the phenomenon of surface plasmon resonance (SPR) are becoming increasingly used in biology and medicine. Their application facilitates exploration in real time progress of binding of biomolecules and identification of agents that specifically interact with biologically active substances immobilized on the biosensor surface (biochips). Special attention is paid to the use of Biosensor analysis in determining the antibody-antigen interaction in the diagnostics of diseases caused by viruses and bacteria. According to WHO, the diseases that are caused by the herpes simplex virus (HSV), take second place (15.8%) after influenza as a cause of death from viral infections. Current diagnostics of HSV infection include PCR and ELISA assays. The latter allows determination the degree of immune response to viral infection and respective stages of its progress. In this regard, the searches for new and available diagnostic methods are very important. This work was aimed to develop Biosensor chip for detection of specific antibodies to HSV-1 in the human blood serum. The proteins of HSV1 (strain US) were used as antigens. The viral particles were accumulated in cell culture MDBK and purified by differential centrifugation in cesium chloride density gradient. Analysis of the HSV1 proteins was performed by polyacrylamide gel electrophoresis and ELISA. The protein concentration was measured using De Novix DS-11 spectrophotometer. The device for detection of antigen-antibody interactions was an optoelectronic two-channel spectrometer ‘Plasmon-6’, using the SPR phenomenon in the Krechman optical configuration. It was developed at the Lashkarev Institute of Semiconductor Physics of NASU. The used carrier was a glass plate covered with 45 nm gold film. Screening of human blood serums was performed using the test system ‘HSV-1 IgG ELISA’ (GenWay, USA). Development of Biosensor chip included optimization of conditions of viral antigen sorption and analysis steps. For immobilization of viral proteins 0.2% solution of Dextran 17, 200 (Sigma, USA) was used. Sorption of antigen took place at 4-8°C within 18-24 hours. After washing of chip, three times with citrate buffer (pH 5,0) 1% solution of BSA was applied to block the sites not occupied by viral antigen. It was found direct dependence between the amount of immobilized HSV1 antigen and SPR response. Using obtained biochips, panels of 25 positive and 10 negative for the content of antibodies to HSV-1 human sera were analyzed. The average value of SPR response was 185 a.s. for negative sera and from 312 to. 1264 a.s. for positive sera. It was shown that SPR data were agreed with ELISA results in 96% of samples proving the great potential of SPR in such researches. It was investigated the possibility of biochip regeneration and it was shown that application of 10 mM NaOH solution leads to rupture of intermolecular bonds. This allows reuse the chip several times. Thus, in this study biosensor chip for detection of specific antibodies to HSV1 was successfully developed expanding a range of diagnostic methods for this pathogen.

Keywords: biochip, herpes virus, SPR

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Authors: Igna Brajevic-Gizdic, Magda Pletikosa Pavić

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Introduction: Research in opiate addiction is increasingly indicating the importance of substitution therapy in opiate addicts. Opiate addiction is a chronic relapsing disease that includes craving as a criterion. Craving has been considered a predictor of a relapse, which is defined as a strong desire with an excessive need to take a substance. The study aimed to measure the intensity of craving using the VAS (visual analog scale) in opioid addicts taking Opioid Substitution Therapy (OST). Method: The total sample compromised of 30 participants in outpatient treatment. Two groups of opiate addicts were considered: Methadone-maintenance and buprenorphine-maintenance addicts. The participants completed the survey questionnaire during the outpatient treatment. Results: The results indicated high levels of cravings in patients during the treatment of OST, which is considered an important destabilization factor in abstinence. Thus, the use of methadone/buprenorphine dose should be considered. Conclusion: These findings provided an objective measurement of methadone /buprenorphine dosage and therapy options. The underdoes of OST can put patients at high risk of relapse, resulting in high levels of craving. Thus, when determining the therapeutic dose of OST, it is crucial to consider patients' cravings. This would achieve stabilization more quickly and avoid relapse in abstinence. Subjective physician assessment and patients' statement are the main criteria to determine OST dosage. Future studies should use larger sample sizes and focus on the importance of intensity craving measurement on OST to objectify methadone /buprenorphine dosage.

Keywords: buprenorphine, craving, heroin addicts, methadone, OST

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Authors: M. Qorbani

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Neuromuscular control of posture as understood through studies of responses to mechanical sudden acceleration automatically has been previously demonstrated in individuals with chronic ankle instability (CAI), but the presence of acute condition has not been previously explored specially in a sudden acceleration. The aim of this study was to determine neuromuscular control pattern in those with and without unilateral acute ankle sprains. Design: Case - control. Setting: University research laboratory. The sinker–card protocol with surface translation was be used as a sudden acceleration protocol with study of EMG upon 4 posture stabilizer muscles in two sides of the body in response to sudden acceleration in forward and backward directions. 20 young adult women in two groups (10 LAS; 23.9 ± 2.03 yrs and 10 normal; 26.4 ± 3.2 yrs). The data of EMG were assessed by using multivariate test and one-way repeated measures 2×2×4 ANOVA (P< 0.05). The results showed a significant muscle by direction interaction. Higher TA activity of left and right side in LAS group than normal group in forward direction significantly be showed. Higher MGR activity in normal group than LAS group in backward direction significantly showed. These findings suggest that compared two sides of the body in two directions for 4 muscles EMG activities between and within group for neuromuscular control of posture in avoiding fall. EMG activations of two sides of the body in lateral ankle sprain (LAS) patients were symmetric significantly. Acute ankle instability following once ankle sprains caused to coordinated temporal spatial patterns and strategy selection.

Keywords: neuromuscular response, sEMG, lateral ankle sprain, posture.

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Authors: Tshimangadzo Jeanette Raedani, Edgar Musie, Afsatou Traore

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Background: Street-vended meats, including chicken, pork, and beef, are popular in urban areas worldwide due to their convenience and affordability. However, these meats often pose a significant risk of foodborne diseases. The high water activity, protein content, and nearly neutral pH of meat create conditions conducive to the growth of pathogenic bacteria. Street foods, particularly meats, are frequently linked to outbreaks of foodborne illnesses due to potential contamination from improper handling and preparation. This study aimed to assess the microbial quality and safety of street-vended ready-to-eat meat sold in the Thohoyandou area. Method: The study involved collecting 168 samples of street-vended meat, split evenly between chicken (n=84) and beef (n=84), from various vendors around Thohoyandou. The samples were randomly selected and transported in sterile conditions to the Department of Food Microbiology at the University of Venda for analysis. Each 10-gram sample was cultured in selective media: MSA for Staphylococcus aureus, EMB for E. coli O157, XLD agar for Salmonella, and Sorbitol McConkey for Shigella. After initial culturing, the presumptive colonies were sub-cultured for purification and identified through Gram staining and biochemical tests, including Catalase, API 20E, Klingler Iron Agar Test, and Vitek 2 system. Antibiotic susceptibility was tested using agents such as Ampicillin, Chloramphenicol, Penicillin, Neomycin, Tetracycline, Streptomycin, and Amoxicillin. Molecular characterization was performed to identify E. coli pathotypes using multiplex PCR. Results: Out of 168 samples tested, 32 (19%) were positive for Staphylococcus spp., with the highest prevalence found in cooked chicken meat. The most common staphylococcus species identified were S. xylosus (13.2%) and S. saprophyticus (10.5%). E. coli was present in 29 (19.3%) of the samples, with the highest prevalence in fried chicken. Antibiotic susceptibility testing showed that 100% of E. coli isolates were resistant to Ampicillin, Tetracycline, and Penicillin, but 100% were susceptible to Neomycin. Staphylococcus spp. isolates were also 100% resistant to Ampicillin and 100% susceptible to Neomycin. The study detected a range of virulence genes in E. coli, with prevalence rates from 13.33% to 86.67%. The identified pathotypes included EPEC, EHEC, ETEC, EAEC, and EIEC, with many isolates showing mixed pathotypes. Conclusion: The study highlighted that the microbial quality and safety of street-vended meats in Thohoyandou are inadequate, rendering them unsafe for consumption. The presence of pathogenic microorganisms in both beef and chicken samples indicates significant risks associated with poor personal hygiene and food preparation practices. This underscores the need for improved monitoring and stricter food safety measures to prevent foodborne diseases and ensure consumer safety.

Keywords: meat, microbial analysis, street vendors, E. coli

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Authors: Feroz A. Shah, M. H. Balkhi

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The study was aimed at to record the distribution and prevalence of various metazoan parasites of fish from hill stream/coldwater fishes of various water bodies of northwest Himalayan region of India. Snow trout (Schizoth oracids) from eutrophic lakes and fresh water streams were collected from January to December 2012, to study the impact of environmental factors on the dynamics and distribution of parasitic infection. The prevalence of helminth parasites was correlated with available physico-chemical parameters including water temperature, pH and dissolved oxygen (DO). The most abundant parasitic infection recorded during this study was Adenoscolex sp. (Cestode parasite) which showed positive correlation with pH (significant p≤0.05) negative correlation with temperature. The Bothriocephalus was having positive correlation with water temperature while as negative correlation was observed with pH and DO. The correlation between Diplozoon sp. and Clinostomum sp. with the physiochemical parameters were non-significant.

Keywords: hill stream fishes, parasites, Western Himalayas, prevelance

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Authors: Destin Kurniawati

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Asthma is one of the deadly diseases in the world. According to the World Health Organization in 2012, 300 million people suffer from asthma of different races and classes. An estimated 250,000 people die because of asthma annually.As well as more than 57% of children and 51% of adults with asthma. There two risk factors for asthma. That risk factors are the host and environmental. One of the environmental factors that can bring asthma is allergens. When an allergen enters the body, the allergen binds to IgE and cause cell granulat- issued several mediators such as histamine, leukotrienes, bradykinin or something like that. This will cause localized edema effect on bronchial walls of small, thick mucous secretions in the bronchioles, and bronchial smooth muscle spasm. Then there will be inflammation of the airways. Methodology this research is by literature. Therefore, to anticipate and cope with asthma is to control environmental factors that serve to minimize allergens and controlling one's intake in the form of antioxidant-rich foods. Foods rich in antioxidants serve to improve lung function and decrease symptoms of the disease of the respiratory tract.

Keywords: asthma, deadly disease, allergen, environmental and food control

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Authors: S. F. Afzali, W. L. Wong

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The epizootic ulcerative syndrome (EUS) causes by the oomycete fungus, Aphanomyces invadans; known to be one of the infectious fish diseases for farmed and wild fishes in fresh and brackish-water from the Asia-pacific region, America and Africa. Although, EUS had been documented by the Office International des Epizooties (OIE) since 1995, hitherto, there is neither standard chemical agents that can be used for successful treatment of this destructive infection in the time of outbreak; nor available vaccine for prevention. Plant-based remedies in controlling fish diseases are gaining much attention recently as an alternative to chemical treatments, which possess negative effects to the environment and human. In present study, Sonneratia alba, a mangrove plant belongs to the Sonneratiaceae family, was screened in vitro and in vivo for its antifungal activity against A. invadans mycelium growth and its effects on fish innate immune system and disease resistant. The in vitro tests was performed using the disc diffusion methods with measurements of minimum inhibitory concentration (MIC) and inhibition zone. For in vivo study, the S. alba extract supplemented diets were administrated at 0.0, 1.0%, 3.0%, and 5.0% on healthy goldfish, Carassius auratus, which challenged with A. invadans zoospores (100 spores/ml). To compare the significant differences in the hematological and immunological parameters obtained from the experiments, the data were analysed using the SPSS. The methanol extract of S. alba effectively inhibited the mycelial growth of A. invadans at a minimum concentration of 1000 ppm for agar and filter paper diffusion experiments. In the agar diffusion test, 500 ppm of the extract inhibited the fungus mycelial growth up to 96 hours after exposure. The mycelial growth from the edge of the pre-inoculated A. invadans agar discs treated with S. alba extracts at concentrations of 100, 500 and 1000 ppm were 15, 8 and 0 mm respectively. The results of the filter paper disc test showed that the S. alba extract at its minimal inhibitory concentration (1000 ppm) has similar qualitative inhibitory effect as malachite green at 1 ppm and formalin at 250 ppm. According to the in vivo tests findings, in the infected fish fed with 3.0% and 5.0% supplementation diet, the numbers of white blood cell and myeloperoxidase activity significantly increased after the second week of treatment. Whilst the numbers of red blood cell significantly decreased in the infected fish fed with 0.0 and 1.0% supplementation diet. After the third week of feeding, significant increases in the total protein, albumin level, lysozyme activity were recorded in the infected fish fed with 3.0% and 5.0% supplementation diet. Also, the enriched diets increased the survival rate as compared to the untreated group that suffered from 90% mortality. The present study indicated that S. alba extract may inhibit the mycelial growth of A. invadans effectively, suggesting an alternative to other chemotherapeutic agents, which brought much environmental and health concerns to the public, for EUS treatment.

Keywords: fungal pathogen, goldfish, organic extract, treatment

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Authors: Tan Yong Sheng Edgar, Yeong Wai Yee

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Age-related macular degeneration (AMD) is one of the leading cause of blindness. It can cause severe visual loss due to damaged retinal pigment epithelium (RPE). RPE is an important component of the retinal tissue. It functions as a transducing boundary for visual perception making it an essential factor for sight. The RPE also functions as a metabolically complex and functional cell layer that is responsible for the local homeostasis and maintenance of the extra photoreceptor environment. Thus one of the suggested method of treating such diseases would be regenerating these RPE cells. As such, we intend to grow these cells using a synthetic scaffold to provide a stable environment that reduces the batch effects found in natural scaffolds. Stiffness of the scaffold will also be investigated to determine the optimal Young’s modulus for cultivating these cells. The cells will be generated into a monolayer cell sheet and their functions such as formation of tight junctions and gene expression patterns will be assessed to evaluate the cell sheet quality compared to a native RPE tissue.

Keywords: RPE, scaffold, characterization, biomaterials, colloids and nanomedicine

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Authors: Rita Yuniatun, Dewi Fadlilah Firdausi, Anida Hanifah, Putrisuvi Nurjannah Zalqis, Erza Nur Afrilia, Akrima Fajrin Nurimani, Andrew Luis Krishna

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Manganese (Mn) is one of the potential contaminants minerals geothermal water. Preliminary studies conducted in Ketenger village, the nearest village with Baturaden hot spring, showed that the concentration of Mn in water supply has exceeded the reference value. Mineral contamination problem in Ketenger village is not only Mn, but also other potential geothermal minerals, such as chromium (Cr), iron (Fe), sulfide (S2-), nickel (Ni), cobalt (Co), and zinc (Zn). It becomes a concern because generally the residents still use ground water as the water source for their daily needs, including drinking and cooking. Therefore, this study aimed to determine the distribution of mineral contamination in drinking water and food and to estimate the health risks possibility from the exposure. Four minerals (Mn, Fe, S2-, and Cr6+) were analyzed in drinking water, carbohydrate sources, vegetables, fishes, and fruits. The test results indicate that Mn concentration in drinking water is 0.35 mg/L, has exceeded the maximum contaminant level (MCL) according to the US EPA (MCL = 0.005 mg/L), whereas other minerals still comply with the standards. In addition, we found that the average of Mn concentration in the carbohydrate sources is quite high (1.87 mg/Kg). Measurement results in Chronic Daily Intake (CDI) and the Risk Quotient (RQ) found that exposure to manganese and other geothermal minerals in drinking water and food are safe from the non-carcinogenic effects in each age group (RQ<1). So, geothermal mineral concentrations in drinking water and food has no effect on non-carcinogenic risk in Ketenger’s residents because of CDI is also influenced by other parameters such as the duration of exposure and the rate of consumption. However, it was found that intake of essential minerals (Mn and Fe) are deficient in every age group. So that, the addition of Mn and Fe intake is recommended.

Keywords: CDI, contaminant, geothermal minerals, manganese, RQ

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Authors: W. Promprom, W. Chatan

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Leguminosae is a large plant family and its members are important for local people utilization in the Northeast of Thailand. This research aimed to survey medicinal plants in this family in Kantharalak Community forest. The plant collection and exploration were made from October 2017 to September 2018. Folk medicinal uses were studied by interviewing villagers and folk medicine healers living around the community forest by asking about local names, using parts, preparation and properties. The results showed that 65 species belonging to 40 genera were found. Among these, 30 species were medicinal plant. The most used plant parts were leaf. Decoction and drinking were mostly preparation method and administration mode used. All medicinal plants could be categorized into 17 diseases/symptoms. Most plant (56.66%) were used for fever. The voucher specimens were deposited in Department of Biology, Faculty of Science, Mahasarakham University, Thailand. Therefore, the data from this study might be widely used by the local area and further scientific study.

Keywords: ethnobotany, ethnophamacology, medicinal plant, taxonomy, utilization

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Authors: Michael Daly

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Background/Aims: The interplay of childhood self-control and early life social background in predicting adult health is currently unclear. We drew on rich data from two large nationally representative cohort studies to test whether individual differences in childhood self-control may: (i) buffer the health impact of social disadvantage, (ii) act as a mediating pathway underlying the emergence of health disparities, or (iii) compensate for the health consequences of socioeconomic disadvantage across the lifespan. Methods: We examined data from over 25,000 participants from the British Cohort Study (BCS) and the National Child Development Study (NCDS). Child self-control was teacher-rated at age 10 in the BCS and ages 7/11 in the NCDS. The Early life social disadvantage was indexed using measures of parental education, occupational prestige, and housing characteristics (i.e. housing tenure, home crowding). A range of health outcomes was examined: the presence of chronic conditions, whether illnesses were limiting, physiological dysregulation (gauged by clinical indicators), mortality, and perceptions of pain, psychological distress, and general health. Results: Childhood self-control and social disadvantage predicted each measure of adult health, with similar strength on average. An examination of mediating factors showed that adult smoking, obesity, and socioeconomic status explained the majority of these linkages. There was no systematic evidence that self-control moderated the health consequences of early social disadvantage and limited evidence that self-control acted as a key pathway from disadvantage to later health. Conclusions: Childhood self-control predicts adult health and may compensate for early life social disadvantage by shaping adult health behaviour and social status.

Keywords: personality and health, social disadvantage, health psychology, life-course development

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Authors: Leyla Esfandiari

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Rapid, sensitive detection of nucleic acid (NA) molecules of specific sequence is of interest for a range of diverse health-related applications such as screening for genetic diseases, detecting pathogenic microbes in food and water, and identifying biological warfare agents in homeland security. Sequence-specific nucleic acid detection platforms rely on base pairing interaction between two complementary single stranded NAs, which can be detected by the optical, mechanical, or electrochemical readout. However, many of the existing platforms require amplification by polymerase chain reaction (PCR), fluorescent or enzymatic labels, and expensive or bulky instrumentation. In an effort to address these shortcomings, our research is focused on utilizing the cutting edge nanotechnology and microfluidics along with resistive pulse electrical measurements to design and develop a cost-effective, handheld and highly-sensitive nanopore-based sensor for point-of-care medical diagnostics.

Keywords: diagnostics, nanopore, nucleic acids, sensor

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Authors: M. Khallaf, R. Khalil, H. Ghetas

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In the present study, V. harveyi and V. alginolyticus were isolated from cultured seabass and seabream at Damietta Governorate, Egypt, during summer season. Isolates were biochemically and molecularly identified using primers for Vhh and Collagenase genes. The most prominent clinical observations of diseased fish were exophthalmia, abdominal distension, and multifocal cutaneous hemorrhagic ulceration on the dorsal musculature and caudal peduncle. Physicochemical characteristics of water samples indicated that the unionized ammonia, nitrate, and hydrogen sulphate concentrations were higher than the acceptable limits. Heavy metals concentrations in water samples exhibited higher concentrations than the permissible levels for fish culture, which was considered as chemical stressors that increase the prevalence of these bacterial diseases. Immune parameters were lower in diseased seabass and seabream than apparently healthy fish. Lesions of different fish organs were identified histopathologically.

Keywords: seabass, seabream, Vibrio alginolyticus, Vibrio harveyi

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Authors: Maedeh Shojaeizadeh, Amirreza Yeganegi

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Nowadays many people lose their lives due to cardiovascular diseases. Inappropriate food habits and lack of exercise expedite deposit process of fatty substances on inner surface of blood arteries. This abnormal lump disturbs uniform blood flow and reduces oxygen delivery to active organs. This work presents a numerical simulation of Non-Newtonian blood flow in a stenosis vessel. The vessel is considered as two dimensional channel and plaque area is modelled as a homogenous porous medium. To simulate blood flow reaction around stenosis region, we use C++ code and solve coupled Cauchy, Darcy, governing continuity and energy equations. The analyses results show that viscosity power (n) plays an important role in flow separation and the size of the eddy at the downstream edge of the plaque. It is also observed that with increasing (n) value, temperature discontinuity and likelihood of vessel rupture declined.

Keywords: blood flow, computational fluid dynamic, porosity, power law fluid

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Authors: Cherif Y., Ghariani R., Derbal S., Farhati S., Ben Dahmen F., Abdallah M.

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Introduction: Tuberculosis (TBC) is a frequent infection and is still a major public health problem in Tunisia. The aim of this work is to focus on diagnostic and therapeutic characteristics of TBC in patients referred to our internal medicine department. Patients and Methods: The study was retrospective and descriptive of a cohort of consecutive cases treated from January 2016 to December 2019, collecting patients with latent or patent TBC. Twenty-eight medical records of adults diagnosed with TBC were reviewed. Results: Twenty-eight patients, including 18 women and 10 men, were diagnosed with TBC. Their mean age is 48 years (range: 22-78 years). Five patients have a medical history of diabetes mellitus, 1 patient was followed for systemic lupus erythematosus treated with corticosteroids and immunosuppressant drugs, and another was treated with corticosteroids for Mac Duffy syndrome. The TBC is latent in 12 cases and patent in 16 cases. The most common symptoms were fever and weight loss and were found in 10 cases, a cough in 2 cases, sputum in 3 cases, lymph nodes in 4 cases, erythema nodosum in 2 cases, and neurological signs in 3 cases. Lymphopenia is noticed in 3 cases and a biological inflammatory syndrome in 18 of the cases. The purified protein derivate reaction was positive in 17 cases, anergic in 3 cases, negative in 5 cases, and not done in 3 cases. The acid-fast bacilli stain culture was strongly positive in one patient. The histopathological study was conclusive in 11 patients and showed granulomatosis with caseous necrosis. TBC was pulmonary in 7 patients, lymph node in 7 cases, peritoneal in 7 cases, digestive in 1 case, neuromeningeal in 3 cases, and thyroïd in 1 case. Seven patients had multifocal TBC. All the patients received anti-tuberculosis treatment with a mean duration of 8 months with no failure or relapse with an average follow-up time of 10.58 months. Conclusion: Diagnosis and management of TBC remain essential to avoid serious complications. The survey is necessary to ensure timely detection and treatment of infected adults to decrease its incidence. The best treatment remains preventive through vaccination and improving social and economic conditions.

Keywords: tuberculosis, infection, autoimmune disease, granulomatosis

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Authors: Sabrina Azzi, Michal Iglewski, Véronique Nabelsi

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Diagnosis error problem is frequent and one of the most important safety problems today. One of the main objectives of our work is to propose an ontological representation that takes into account the diagnostic criteria in order to improve the diagnostic. We choose pneumonia disease since it is one of the frequent diseases affected by diagnosis errors and have harmful effects on patients. To achieve our aim, we use a semi-automated method to integrate diverse knowledge sources that include publically available pneumonia disease guidelines from international repositories, biomedical ontologies and electronic health records. We follow the principles of the Open Biomedical Ontologies (OBO) Foundry. The resulting ontology covers symptoms and signs, all the types of pneumonia, antecedents, pathogens, and diagnostic testing. The first evaluation results show that most of the terms are covered by the ontology. This work is still in progress and represents a first and major step toward a development of a diagnosis decision support system for pneumonia.

Keywords: Clinical decision support system, Diagnostic errors, Ontology, Pneumonia

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Authors: Dandan Shen, Hui-zhu Wang, Xi Yu, LiLi Gui, Xiao Wei, Xiao-yan Jiang, Da-wei Wang, Min Hong

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Yu-ping-feng-san (YPFS) is a clinical medicine for asthma and other allergic diseases, but the mechanism of YPFS on relapse of allergy is unclear. Currently, people come to realize the epithelial cells(EC) play a key role in stimulating and regulating local immune response. The study of thymic stromal lymphopoietin（TSLP derived from EC provides an important evidence that the EC can regulate immune response to stimulate allergic response. In this study, we observed the effect of YPFS on TSLP in vivo and in vitro. We established a method by using bronchial epithelial cells (16HBE) for screening potential bioactive components by HPLC-MS in YPFS and then analyzed the components in serum containing YPFS by UPLC-MS. The results showed that YPFS could decrease TSLP protein level in OVA-sensitized mice and 16HBE cells. Five components combing with the 16HBE cells were both detected in the serum.

Keywords: TSLP, bronchial epithelial cells, cell-binding, drug-containing serum

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Authors: Kamsiah Jaarin, Yusof Kamisah, Faizah Othman Nurul Akmal Muhammad, Zakiah Jubri, Qodriyah Mohd Saad, Srijit Das

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Forty (40) normotensive adult male Sprague-Dawley rats aged three months weighing 180-200 g were divided into 4 groups with 10 rats per group: (1) normotensive control; (2) hypertensive rats; (3) hypertensive rats treated with Nigella sativa (2.5 ml/kg/day); and (4) hypertensive rats treated with nicardipine (5 mg/kg/day). After acclimatization, the hypertensive rats of the group 2, 3 and 4 were induced to be hypertensive by giving NW–nitro-L-arginine methyl ester (L-NAME; 30 mg/kg/day) in their drinking water for consecutive 7 days. After one week, rats in the group 3 were given a daily oral dose of 2.5 ml/kg/day of Nigella sativa (NS) by oral gavage. Rats in the group 4 were given nicardipine (5 mg/kg/day) via oral gavages. All rats in this study received L-NAME continuously throughout the treatment duration. The blood pressure will be measured pre-treatment and weekly for 8 weeks using power lab. Blood was taken before and at the end of study for measurement of nitric oxide. At the end of 8 weeks, the rats are sacrificed and descending thoracic aorta was disserted for measurement of vascular reactivity, and intracellular adhesion molecules (ICAM-1) and vascular cell adhesion molecules (VCAM-1). Nigella sativa reduced both systolic and diastolic BP compared to control and L-name group. The BP lowering effect of NS was comparable to nicardipine a calcium antagonist. The blood pressure lowering effect of NS was accompanied with an increasing relaxation response to nitroprusside and acetylcholine and reducing vasoconstriction response to epinephrine. L-NAME and nicardipine on the other hand, reduced plasma nitric oxide concentration. In contrast, NS increased NO concentration. However, Nigella sativa had no significant effect on aortic VCAM- 1 and ICAM-1 expression. In conclusion; Nigella sativa oil reduces both systolic and diastolic blood pressure in L-NAME treated rats. The antihypertensive effect of NS was comparable to nicardipine. The BP lowering effect may be mediated via stimulating nitric oxide release from vascular endothelium.

Keywords: Nigella sativa, ICAM, VCAM, blood pressure, vascular reactivity

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Authors: Omid Ghollipoor Bashiri, Farzam Hatefi

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Dichlorvos a synthetic organophosphate poisons are used as insecticide. These toxins can be used insecticides in agriculture and medicine for destruction and/or eradication of ectoparasites of animals. Studies have shown that Dichlorvos creation seizure effects in different animals. Amlodipine, dihydropyridine calcium channel blockers, widely used for treatment of cardiovascular diseases. Studies have shown that the calcium channel blockers are anticonvulsant effects in different animal models. The aim of this study was to determine the effect of Amlodipine on Dichlorvos-induced seizures in mice. In this experiment, the animals were received different doses of Amlodipine (2.5, 5, 10, 20 and 40 mg/ kg b.wt.) intraperitoneally 30 min before intraperitoneal injection of Dichlorvos (50 mg/kg b.wt). After Dichlorvos injection, clonic and tonic seizures, and finally was the fate was investigated. Results showed that Amlodipine dose-dependently reduced the severity of Dichlorvos-induced seizures, so that Amlodipine at a dose of 5mg (The lowest, p<0.05) and 40 mg/kg b.wt. (The highest, p<0.001) which had anticonvulsant effects. The anticonvulsant activity of Amlodipine suggests that possibly due to the antagonistic effect on voltage-dependent calcium channel.

Keywords: dichlorvos, amlodipine, seizures, mice

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Authors: Alaa Abdellatif, Gabrièle Breda

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Background. Advanced therapy medicinal products (ATMPs) are innovative therapies that mainly target orphan diseases and high unmet medical needs. ATMP includes gene therapy medicinal products (GTMP), somatic cell therapy medicinal products (CTMP), and tissue-engineered therapies (TEP). Since legislation opened the way in 2007, 25 ATMPs have been approved in the EU, which is about the same amount as the U.S. Food and Drug Administration. However, not all of the ATMPs that have been approved have successfully reached the market and retained their approval. Objectives. We aim to understand all the factors limiting the market access to very promising therapies in a systemic approach, to be able to overcome these problems, in the future, with scientific, regulatory and commercial innovations. Further to recent reviews that focus either on specific countries, products, or dimensions, we will address all the challenges faced by ATMP development today. Methodology. We used mixed methods and a multi-level approach for data collection. First, we performed an updated academic literature review on ATMP development and their scientific and market access challenges (papers published between 2018 and April 2023). Second, we analyzed industry feedback from cell and gene therapy webinars and white papers published by providers and pharmaceutical industries. Finally, we established a comparative analysis of the regulatory guidelines published by EMA and the FDA for ATMP approval. Results: The main challenges in bringing these therapies to market are the high development costs. Developing ATMPs is expensive due to the need for specialized manufacturing processes. Furthermore, the regulatory pathways for ATMPs are often complex and can vary between countries, making it challenging to obtain approval and ensure compliance with different regulations. As a result of the high costs associated with ATMPs, challenges in obtaining reimbursement from healthcare payers lead to limited patient access to these treatments. ATMPs are often developed for orphan diseases, which means that the patient population is limited for clinical trials which can make it challenging to demonstrate their safety and efficacy. In addition, the complex manufacturing processes required for ATMPs can make it challenging to scale up production to meet demand, which can limit their availability and increase costs. Finally, ATMPs face safety and efficacy challenges: dangerous adverse events of these therapies like toxicity related to the use of viral vectors or cell therapy, starting material and donor-related aspects. Conclusion. As a result of our mixed method analysis, we found that ATMPs face a number of challenges in their development, regulatory approval, and commercialization and that addressing these challenges requires collaboration between industry, regulators, healthcare providers, and patient groups. This first analysis will help us to address, for each challenge, proper and innovative solution(s) in order to increase the number of ATMPs approved and reach the patients

Keywords: advanced therapy medicinal products (ATMPs), product development, market access, innovation

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Authors: Sana Mohammad Jafar

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Salmonella is one of the major causes of foodborne diseases throughout the world. Shrimp are an important commodity in world fishery trade. The microbiological quality of shrimp must be evaluated for assurance of shrimp. The aim of this study was to evaluate the microbiological quality and to determine the prevalence of Salmonella in shrimp sold in Khuzestan province. In this study, a total of 245 samples of shrimp sold in Khuzestan province were tested for Salmonella prevalence and total microbial population. The mean aerobic bacterial count in 50.2% of samples was 2200, in 29.8% of samples was 13,600, in 20% of samples was 36,700, and the mean aerobic bacterial count in the total samples was 20,000. (20,000 cfu/cc). Of the total samples, 33 samples were positive for Salmonella and the prevalence of Salmonella was determined 13.4%. These results indicate the possibility that shrimp contribute to foodborne infections. The improvement of shrimp quality is an important issue, and shrimp before consuming should be washed with water containing chlorine, with the aim of increasing safety. In addition, it should be avoided to eat shrimp as raw or not cooked properly.

Keywords: determination, total microbial, Salmonella, shrimp

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Authors: Rubaiyea Uddin, Rebecca Taylor, Emily Levesque

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The hippocampus, located in the limbic system, is most commonly known for its role in memory and spatial navigation (as cited in Brain Reward and Pathways). It maintains an especially important role in specifically episodic and declarative memory. The hippocampus has also recently been linked to dopamine, the reward pathway’s primary neurotransmitter. Since research has found that dopamine also contributes to memory consolidation and hippocampal plasticity, this neurotransmitter is potentially responsible for contributing to the hippocampus’s role in memory formation. In this experiment we tested to see the effect of tactile cues on spatial navigation for eight different mice. We used a radial arm that had one designated “reward” arm containing sucrose. The presence or absence of bedding was our tactile cue. We attempted to see if the memory of that cue would enhance the mice’s memory of having received the reward in that arm. The results from our study showed there was no significant response from the use of tactile cues on spatial navigation on our 129 mice. Tactile cues therefore do not influence spatial navigation.

Keywords: mice, radial arm maze, memory, spatial navigation, tactile cues, hippocampus, reward, sensory skills, Alzheimer's, neuro-degenerative diseases

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Authors: Qunying Yuan, Manjula Bomma, Adrian Rhoden, Zhigang Xiao

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Selenium is an essential micronutrient for all mammals and plays an important role in maintaining human physiological functions. The potential applications of selenium as food supplements, cancer-prevention, antimicrobial and anti-inflammatory agents have been investigated in biomedicine and food sciences. Nanoscale of selenium is of particular interest due to its better biocompatibility, higher bioavailability, lower toxicity, more homogeneous distribution, and presumptive controlled release of substances. The objective of this study is to explore whether selenium nanoparticle (SeNP) has the potential to be used as a food preservative to reduce food spoilage. SeNPs were synthesized through ascorbic acid reduction of sodium selenite using the bovine serum albumin (BSA) as capping and stabilizing agent. The chemically synthesized SeNPs had a spherical conformation and a size of 22.8 ± 4.7 nm. FTIR analysis confirmed that the nanoparticles were covered with BSA. We further tested the antimicrobial activity of these SeNPs against common food-borne bacteria. Colony forming unit assay showed that SeNPs exhibited good inhibition on the growth of Listeria Monocytogens (ATCC15313), Staphylococcus epidermidis (ATCC 700583) starting at 0.5µg/mL, but only a moderate inhibitory effect on the growth of Staphylococcus aureus (ATCC12600) and Vibrio alginolyticus (ATCC 33787) at a concentration higher than 10µg/mL and 2.5µg/mL, respectively. There was a mild effect against the growth Salmonella enterica (ATCC19585) when the concentration reached 15µg/mL. No inhibition was observed in the growth of Enterococcus faecalis (ATCC 19433). Surprisingly, SeNPs appeared to promote the growth of Vibrio parahaemolyticus (ATCC43996) and Salmonella enterica (ATCC49284) at 30 µg/mL and above. Our preliminary data suggested that the chemically synthesized SeNPs may be able to inhibit some food-borne bacteria, and SeNP as a food preservative should be used with caution. We will explore the mechanisms of the inhibitory action of chemically synthesized SeNPs on bacterial growth and whether the SeNPs are able to inhibit the development of biofilm and antibiotic resistance.

Keywords: antimicrobial, food-borne bacteria, nanoparticles, selenium

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Authors: A. A. El Maghrbi

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The control of vectors like mosquitoes based on the application of chemical insecticides but due to its adverse effect on the environment, and development of resistance by most of species of mosquitoes including vectors of important diseases. Ethanol and acetone extracts of nine species of plants (Allium tuberosum, Apium leptophylum, Carica papaya, Cymbopogon citratus, Euphorbia cotinofolia, Melia azedarach, Ocimum canum, Ricinus common, and Tagetes erecta) were tested in respect of their influence on the eggs and larvae of Culex quinquifasciatus in concentration 100, 10 and 1 mg/L. In relation to the survival of larvae, ethanol extract of O. canum and acetone extract of A.tuberosum in 100 mg/L have larvicide activity against L4 of Cx. quinquifasciatus. For hatching of eggs, ethanol and acetone extract of A.tuberosum (100 and 10 mg/L) and acetone extract of C.citratus (100 mg/L) produced reduction in the number of eggs hatched of Cx. quinquifasciatus. Our results indicate that each extract of the plant have potential to control mosquito population and suggest that further studies are needed in this field.

Keywords: Cx. quinquefasciatus, plant extract, ethanol, acetone, larvae, eggs

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Authors: Lohendy Munoz-Vargas, Stephen O. Opiyo, Rose Digianantonio, Michele L. Williams, Asela Wijeratne, Gregory Habing

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Non-typhoidal Salmonella enterica is a zoonotic pathogen with critical importance in animal and public health. The persistence of Salmonella on farms affects animal productivity and health, and represents a risk for food safety. The intestinal microbiota plays a fundamental role in the colonization and invasion of this ubiquitous microorganism. To overcome the colonization resistance imparted by the gut microbiome, Salmonella uses invasion strategies and the host inflammatory response to survive, proliferate, and establish infections with diverse clinical manifestations. Cattle serve as reservoirs of Salmonella, and periparturient cows have high prevalence of Salmonella shedding; however, to author`s best knowledge, little is known about the association between the gut microbiome and the onset of Salmonella shedding during the periparturient period. Thus, the objective of this study was to assess the association between changes in bacterial communities and the onset of Salmonella shedding in cattle approaching parturition. In a prospective cohort study, fecal samples from 98 dairy cows originating from four different farms were collected at four time points relative to calving (-3 wks, -1 wk, +1 wk, +3 wks). All 392 samples were cultured for Salmonella. Sequencing of the V4 region of the 16S rRNA gene using the Illumina platform was completed to evaluate the fecal microbiome in a selected sample subset. Analyses of microbial composition, diversity, and structure were performed according to time points, farm, and Salmonella onset status. Individual cow fecal microbiomes, predominated by Bacteroidetes, Firmicutes, Spirochaetes, and Proteobacteria phyla, significantly changed before and after parturition. Microbial communities from different farms were distinguishable based on multivariate analysis. Although there were significant differences in some bacterial taxa between Salmonella positive and negative samples, our results did not identify differences in the fecal microbial diversity or structure for cows with and without the onset of Salmonella shedding. These data suggest that determinants other than the significant changes in the fecal microbiome influence the periparturient onset of Salmonella shedding in dairy cattle.

Keywords: dairy cattle, microbiome, periparturient, Salmonella

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Authors: Yifat Koren Carmi, Abed Agbarya, Hazem Khamaisi, Raymond Farah, Yelena Shechtman, Roman Korobochka, Jacob Gopas, Jamal Mahajna

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Ovarian cancer (OC), the second most common form of gynecological malignancy, has a poor prognosis and is frequently identified in its late stages. The recommended treatment for OC typically includes a platinum-based chemotherapy, like carboplatin. Nonetheless, OC treatment has proven challenging due to toxicity and development of acquired resistance to therapy. Chemoresistance is a significant obstacle to a long-lasting response in OC patients, believed to arise from alterations within the cancer cells as well as within the tumor microenvironments (TME). Malignant ascites is a presenting feature in more than one-third of OC patients. It serves as a reservoir for a complex mixture of soluble factors, metabolites, and cellular components, providing a pro-inflammatory and tumor-promoting microenvironment for the OC cells. Malignant ascites is also associated with metastasis and chemoresistance. In an attempt to elucidate the role of TME in chemoresistance of OC, we monitored the ability of soluble factors derived from ascites fluids to affect platinum sensitivity of OC cells. This research, compared ascites fluids from non-malignant cirrhotic patients to those from OC patients in terms of their ability to alter the platinum sensitivity of OC cells. Our findings indicated that exposure to OC ascites induces platinum chemoresistance on OC cells in 11 out of 13 cases (85%). In contrast, 75% of cirrhosis ascites (3 out of 4) failed to confer platinum chemoresistance to OC cells. Cytokine array analysis revealed that IL-6, and to a lesser extent HGF were enriched in OC ascites, whereas IL-22 was enriched in cirrhosis ascites. Pharmaceutical inhibitors that target the IL-6/JAK signaling pathway were mildly effective in overcoming the platinum chemoresistance induced by malignant ascites. In contrast, Crizotinib an HGF/c-MET inhibitor, and 2-hydroxyestradiol (2HE2) were effective in restoring platinum chemoresistance to OC. Our findings demonstrate the importance of OC ascites in supporting platinum chemoresistance as well as the potential of a combination therapy with Crizotinib and the estradiol metabolite 2HE2 to regain OC cells chemosensitivity.

Keywords: ovarian cancer, platinum chemoresistance, malignant ascites, tumor microenvironment, IL-6, 2-hydroxyestradiol, HGF, crizotinib

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Authors: G. Lambe, D. Mansukhani, A. Shetty, S. Khodaiji, C. Rodrigues, F. Kapadia

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Introduction: Sepsis is known to cause impairment of both innate and adaptive immunity and involves an early uncontrolled inflammatory response, followed by a protracting immunosuppression phase, which includes decreased expression of cell receptors, T cell anergy and exhaustion, impaired cytokine production, which may cause high risk for secondary infections due to reduced response to antigens. Although human cytomegalovirus (CMV) is widely recognized as a serious viral pathogen in sepsis and immunocompromised patients, the incidence of CMV reactivation in patients with sepsis lacking strong evidence of immunosuppression is not well defined. Therefore, it is important to determine an association between CMV reactivation and sepsis-induced immunosuppression. Aim: To determine the association between incidence of CMV reactivation and immune modulation in sepsis-induced immunosuppression with time. Material and Methods: Ten CMV-seropositive adult patients with severe sepsis were included in this study. Blood samples were collected on Day 0, and further weekly up to 21 days. CMV load was quantified by real-time PCR using plasma. The expression of immunosuppression markers, namely, HLA-DR, PD-1, and regulatory T cells, were determined by flow cytometry using whole blood. Results: At Day 0, no CMV reactivation was observed in 6/10 patients. In these patients, the median length for reactivation was 14 days (range, 7-14 days). The remaining four patients, at Day 0, had a mean viral load of 1802+2599 copies/ml, which increased with time. At Day 21, the mean viral load for all 10 patients was 60949+179700 copies/ml, indicating that viremia increased with the length of stay in the hospital. HLA-DR expression on monocytes significantly increased from Day 0 to Day 7 (p = 0.001), following which no significant change was observed until Day 21, for all patients except 3. In these three patients, HLA-DR expression on monocytes showed a decrease at elevated viral load (>5000 copies/ml), indicating immune suppression. However, the other markers, PD-1 and regulatory T cells, did not show any significant changes. Conclusion: These preliminary findings suggest that CMV reactivation can occur in patients with severe sepsis. In fact, the viral load continued to increase with the length of stay in the hospital. Immune suppression, indicated by decreased expression of HLA-DR alone, was observed in three patients with elevated viral load.

Keywords: CMV reactivation, immune suppression, sepsis immune modulation, CMV viral load

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