Search results for: colon targeting

Authors: Molnar Catalina, Lexi Frankel, Amalia Ardeljan, Enoch Kim, Marissa Dallara, Omar Rashid

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Introduction: Clostridium difficile (C. diff) is a toxin-producing bacteria that can cause diarrhea and colitis. U.S. Center for Disease Control and Prevention revealed that C. difficile infection (CDI) has increased from 31 cases per 100,000 persons per year in 1996 to 61 per 100,000 in 2003. Approximately 500,000 cases per year occur in the United States. After exposure, the bacteria colonize the colon, where it adheres to the intestinal epithelium where it produces two toxins: TcdA and TcdB. TcdA affects the intestinal epithelium, causing fluid secretion, inflammation, and tissue necrosis, while TcdB acts as a cytotoxin purpose of this study was to evaluate the association between C diff infection and bronchial lung cancer development. Methods: Using ICD- 9 and ICD-10 codes, the data was provided by a Health Insurance Portability and Accountability Act (HIPAA) compliant national database to assess the patients infected with C diff as opposed to the non-infected patients. The Holy Cross Health, Fort Lauderdale, granted access to the database for the purpose of academic research. Patients were matched for age and Charlson Comorbidity Index (CCI). Standard statistical methods were used. Results: Bronchial lung cancer occurrence in the population not infected with C diff infection was 4741, as opposed to the population infected with C. diff, where 2039 cases of lung cancer were observed. The difference was statistically significant (p-value < 2.2x10^e-16), which reveals that C diff might be protective against bronchial lung cancer. The data was then matched by treatment to create to minimize the effect of treatment bias. Bronchial cancer incidence was 422 and 861 in infected vs. non-infected (p-value of < 2.2x10^e-16), which once more indicates that C diff infection could be beneficial in diminishing bronchial cancer development. Conclusion: This retrospective study conveys a statistical correlation between C diff infection and decreased incidence of lung bronchial cancer. Further studies are needed to comprehend the protective mechanisms of C. Diff infection on lung cancer.

Keywords: C. diff, lung cancer, protective, microbiology

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Authors: Min-Chien Su, Tzu-Hsuan Hsu, Guan-Xuan Wu, Shyh-Ming Kuo

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Lung cancer is one of the clinically challenging malignant diseases worldwide. For efficient therapeutics in cancer, combination therapy has developed to acquire a better outcome. PLK-1 was one of the major factors affecting cell mitosis in cancer cells, its inhibitor Bi6727 was proven effective in treating several different cancers namely oral cancer, colon cancer and lung cancer. Despite its low toxicity toward normal cells compared to traditional chemotherapy, it is still yet to be evaluated in detail. Livistona Chinensis (LC) is a Chinese herb that used as a traditional prescription to treat lung cancer. Due to the uncertainty of the efficacy of LC, we utilized a water extraction method to extract the Livistona Chinensis and then lyophilized into powder for further study. In this study we investigated the antiproliferation activities of Bi6727 and LC extracts (LCE) on A549 non-small lung cancer cells. The IC50 of Bi6727 and LCE on A549 are 60 nM and 0.8 mg/mL, respectively. The fluorescent staining images shown nucleolus damage in cells treated with Bi6727 and mitochondrial damage after treated with LCE. A549 cells treated with Bi6727 and LCE showed increased expression of Bax, Caspase-3 and Caspase-9 proteins from Western blot assay. LCE also inhibited A549 cells growth keeping cells at G2-M phase from cell cycle assay. Apoptosis assay results showed that LCE induced late apoptosis of A549 cells. JC-1 assay showed that the mitochondria damaged at the LCE concentration of 0.4 mg/mL. In our preliminary anti-proliferation test of combined LCE and Bi-6727 on A549 cells, we found a dramatically decrease in proliferation after treated with LCE first for 24-h and then Bi-6727 for extra 24-h. This was an important finding regarding synergistic anti-proliferation effect of these drugs, However, the usage, the application sequence of LCE and Bi-6727 on A549 cells and their related mechanisms still need to be evaluated. In summary, the drugs exerted anti-proliferation effect on A549 cells independently. We hopefully combine the usage of these two drugs will bring a different and potential outcome in treating lung cancer.

Keywords: anti-proliferation, A549, Livistona Chinensis fruit extracts, PLK-1 inhibitor

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Authors: Prasamsha Panta, Da Yeon Kim, Ja Yong Jang, Min Jae Kim, Jae Ho Kim, Moon Suk Kim

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Introduction: Among the many anticancer drugs used clinically, doxorubicin (Dox), was one of widely used drugs to treat many types of solid tumors such as liver, colon, breast, or lung. Intratumoral injection of chemotherapeutic agents is a potentially more effective alternative to systemic administration because direct delivery of the anticancer drug to the target may improve both the stability and efficacy of anticancer drugs. Injectable in situ-forming gels have attracted considerable attention because they can achieve site specific drug delivery, long term action periods, and improved patient compliance. Objective: Objective of present study is to confirm clinical benefit of intratumoral chemotherapy using injectable in situ-forming poly(ethylene glycol)-b-polycaprolactone diblock copolymer (MP) and Dox with increase in efficacy and reducing the toxicity in patients with cancer diseases. Methods and methodology: We prepared biodegradable MP hydrogel and measured viscosity for the evaluation of thermo-sensitive property. In vivo antitumor activity was performed with normal saline, MP only, single free Dox, repeat free Dox, and Dox-loaded MP gel. The remaining amount of Dox drug was measured using HPLC after the mouse was sacrified. For cytotoxicity studies WST-1 assay was performed. Histological analysis was done with H&E and TUNEL processes respectively. Results: The works in this experiment showed that Dox-loaded MP have biodegradable drug depot property. Dox-loaded MP gels showed remarkable in vitro cytotoxicity activities against cancer cells. Finally, this work indicates that injection of Dox-loaded MP allowed Dox to act effectively in the tumor and induced long-lasting supression of tumor growth. Conclusion: This work has examined the potential clinical utility of intratumorally injected Dox-loaded MP gel, which shows significant effect of higher local Dox retention compared with systemically administered Dox.

Keywords: injectable in-situ forming hydrogel, anticancer, doxorubicin, intratumoral injection

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Authors: Sarbjit Singh, Amit Kumar Lal

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In India there is no governing body to control advertisement apart from ASCI due to which most of the companies are targeting children in their advertisements that have a negative impact on their behaviour. The main purpose of this research paper is to find out the impact of the television advertisement on the behaviour of the children as observed and reported by parents. The exploratory research design is adopted by using in-depth interviews with 20 parents in various cities of Punjab on the basis semi-structured interviews a self-administered structured Questionnaire was developed for data collection. Exploratory factor analysis using varimax rotation is used to analyse the data from 100 parents from the conjoint cities of Punjab. (Jalandhar, Amritsar and Ludhiana) The finding suggests that children demand those products which are more advertised. Parents believe that television advertisements are affecting the study of their children. Moreover, the children are becoming more violent, stubborn and rebellious. They try to start copying from the advertisements and indulge in bad habits. Children demand, nag and pester their parents to purchase the advertised product. This research paper would help advertisers to understand children behaviour towards advertisements and more over what should be done to control the negative impact of advertisement on children. Advertisers can also understand the parental perception towards advertisement.

Keywords: advertisement, consumer behaviour, children perception, teen marketing

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Authors: A. Beatti, L. Chipchase, A. Rayner, T. Souvlis

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The aims of this study were to investigate the depth of interferential current (IFC) penetration through soft tissue and to investigate the area over which IFC spreads during clinical application. Premodulated IFC and ‘true’ IFC at beat frequencies of 4, 40 and 90Hz were applied via four electrodes to the distal medial thigh of 15 healthy subjects. The current was measured via three Teflon coated fine needle electrodes that were inserted into the superficial layer of skin, then into the subcutaneous tissue (≈1 cm deep) and then into muscle tissue (≈2 cm deep). The needle electrodes were placed in the middle of the four IFC electrodes, between two channels and outside the four electrodes. Readings were taken at each tissue depth from each electrode during each treatment frequency then digitized and stored for analysis. All voltages were greater at all depths and locations than baseline (p < 0.01) and voltages decreased with depth (P=0.039). Lower voltages of all currents were recorded in the middle of the four electrodes with the highest voltage being recorded outside the four electrodes in all depths (P=0.000).For each frequency of ‘true’ IFC, the voltage was higher in the superficial layer outside the electrodes (P ≤ 0.01).Premodulated had higher voltages along the line of one circuit (P ≤ 0.01). Clinically, IFC appears to pass through skin layers to depth and is more efficient than premodulated IFC when targeting muscle tissue.

Keywords: electrotherapy, interferential current, interferential therapy, medium frequency current

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Authors: Jasna Čanadanović-Brunet, Lidija Jevrić, Gordana Ćetković, Vesna Tumbas Šaponjac, Jelena Vulić, Slađana Stajčić

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Wheat contains high amount of nutrients such as dietary fiber, resistant starch, vitamins, minerals and microconstituents, which are building blocks of body tissues, but also help in the prevention of diseases such as cardiovascular disease, cancer and diabetes. Sprouting enhances the nutritional value of whole wheat through biosynthesis of tocopherols, polyphenols and other valuable phytochemicals. Since the nutritional and sensory benefits of germination have been extensively documented, using of sprouted grains in food formulations is becoming a trend in healthy foods. The present work addressed the possibility of using freeze-dried sprouted wheat powder, obtained from spelt-wheat cv. ‘Nirvana’ (Triticum spelta L.) and winter wheat cv. ‘Simonida’ (Triticum aestivum L. ssp. vulgare var. lutescens), as a source of phytochemicals, to improve the functional status of the consumer. The phytochemicals' content (total polyphenols, flavonoids, chlorophylls and carotenoids) and biological activities (antioxidant activity on DPPH radicals and antiinflammatory activity) of sprouted wheat powders were assessed spectrophotometrically. The content of flavonoids (216.52 mg RE/100 g), carotenoids (22.84 mg β-carotene/100 g) and chlorophylls (131.23 mg/100 g), as well as antiinflammatory activity (EC50=3.70 mg/ml) was found to be higher in sprouted spelt-wheat powder, while total polyphenols (607.21 mg GAE/100 g) and antioxidant activity on DDPPH radicals (EC50=0.27 mmol TE/100 g) was found to be higher in sprouted winter wheat powders. Simulation of gastro-intestinal digestion of sprouted wheat powders clearly shows that intestinal digestion caused a higher release of polyphenols than gastric digestion for both samples, which indicates their higher bioavailability in the colon. The results of the current study have shown that wheat sprouts can provide a high content of phytochemicals and considerable bioactivities. Moreover, data reported show that they contain a unique pattern of bioactive molecules, which make these cereal sprouts attractive functional foods for a health-promoting diet.

Keywords: wheat, sprouts, phytochemicals, bioactivity

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Authors: Z. Kolacinski, L. Szymanski. G. Raniszewski, D. Koza, L. Pietrzak

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Magnetic Bio-Nano-Fluid (BNF) can be composed of a buffer fluid such as plasma and magnetic nanoparticles such as iron, nickel, cobalt and their oxides. However iron is one of the best elements for magnetization by electromagnetic radiation. It can be used as a tool for medical diagnosis and treatment. Radio frequency (RF) radiation is able to heat iron nanoparticles due to magnetic hysteresis. Electromagnetic heating of iron nanoparticles and ferro-fluids BNF can be successfully used for non-invasive thermal ablation of cancer cells. Moreover iron atoms can be carried by carbon nanotubes (CNTs) if iron is used as catalyst for CNTs synthesis. Then CNTs became the iron containers and they screen the iron content against oxidation. We will present a method of CNTs addressing to the required cells. For thermal ablation of cancer cells we use radio frequencies for which the interaction with human body should be limited to minimum. Generally, the application of RF energy fields for medical treatment is justified by deep tissue penetration. The highly iron doped CNTs as the carriers creating magnetic fluid will be presented. An excessive catalyst injection method using electrical furnace and microwave plasma reactor will be presented. This way it is possible to grow the Fe filled CNTs on a moving surface in continuous synthesis process. This also allows producing uniform carpet of the Fe filled CNTs carriers. For the experimental work targeted to cell ablation we used RF generator to measure the increase in temperature for some samples like: solution of Fe2O3 in BNF which can be plasma-like buffer, solutions of pure iron of different concentrations in plasma-like buffer and in buffer used for a cell culture, solutions of carbon nanotubes (MWCNTs) of different concentrations in plasma-like buffer and in buffer used for a cell culture. Then the targeted therapies which can be effective if the carriers are able to distinguish the difference between cancerous and healthy cell’s physiology are considered. We have developed an approach based on ligand-receptor or antibody-antigen interactions for the case of colon cancer.

Keywords: cancer treatment, carbon nano tubes, drag delivery, hyperthermia, iron

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Authors: Fatima Ali Abbass, Hassan Ibrahim Rkein

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The number of entities worldwide that currently accept digital currency as payment is increasing; however, digital currency still is not widely accepted as a medium of exchange, nor they represent legal tender. At the same time, this makes accounting for cryptocurrency, as cash (Currency) is not possible under IAS 7 and IAS 32, Cryptocurrency also cannot be accounted for as Financial Assets at fair value through profit or loss under IFRS 9. Therefore, this paper studies the possible means to account for Cryptocurrency, since, as of today, there is not yet an accounting standard that deals with cryptocurrency. The request to have a specific accounting standard is increasing from top accounting firms and from professional accounting bodies. This study uses a mixture of qualitative and quantitative analysis in its quest to explore the best possible way to account for cryptocurrency. Interviews and surveys were conducted targeting accounting professionals. This study highlighted the deficiencies in the current way of accounting for Cryptocurrency as intangible Assets with an indefinite life. The deficiency becomes well highlighted, as the asset will then be subject to impairment, where under GAAP, only depreciation in the value of the intangible asset is recognized. On the other hand, appreciation in the value of the asset is ignored, and this prohibits the reporting entity from showing the true value of the cryptocurrency asset. This research highlights the gap that arises due to using accounting standards that are not specific for Cryptocurrency and this study confirmed that there is an urgent need to call upon the accounting standards setters (IASB and FASB) to issue accounting standards specifically for Cryptocurrency.

Keywords: cryptocurrency, accounting, IFRS, GAAP, classification, measurement

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Authors: Feng Zhang, Li Chen, Desong Kong, Xiaoping Zhang, Xiaojing Zhu, Yin Lu, Shizhong Zheng

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Sinusoidal pathological angiogenesis is a novel therapeutic target for liver fibrosis. We demonstrated that curcumin ameliorated fibrotic injury and sinusoidal angiogenesis in rat liver with fibrosis caused by carbon tetrachloride. Curcumin reduced the expression of angiogenic markers in fibrotic liver. Experiments in vitro showed that the viability and vascularization of rat liver sinusoidal endothelial cells (LSECs) were not impaired by curcumin. Further investigations showed that curcumin inhibited VEGF expression in hepatic stellate cells (HSCs) by disrupting PDGF-βR/ERK and mTOR pathways. HSC motility and vascularization were also suppressed by curcumin via blocking PDGF-βR/FAK/RhoA cascade. Gain- or loss-of-function analyses revealed that activation of PPARγ was required for curcumin to inhibit angiogenic properties of HSCs. We concluded that curcumin attenuated sinusoidal angiogenesis in liver fibrosis possibly by targeting HSCs via a PPARγ activation-dependent mechanism. PPARγ could be a target molecule for reducing pathological angiogenesis during liver fibrosis.

Keywords: angiogenesis, hepatic stellate cell, curcumin, peroxisome proliferator-activated receptor-γ

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Authors: M. Sneha, N. Meenakshi Sundaram

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In recent times, magnetic hyperthermia is used for cancer treatment as a tool for active targeting of delivering drugs to the targeted site. It has a potential advantage over other heat treatment because there is no systemic buildup in organs and large doses are possible. The aim of this study is to develop a suitable magnetic biomaterial that can destroy the cancer cells as well as induce bone regeneration. In this work, the composite material was synthesized in two-steps. First, porous iron oxide nano needles were synthesized by hydrothermal process. Second, the hydroxyapatite, were synthesized from natural calcium (i.e., egg shell) and inorganic phosphorous source using wet chemical method. The crystalline nature is confirmed by powder X-ray diffraction analysis (XRD). Thermal analysis and the surface area of the material is studied by Thermo Gravimetric Analysis (TGA), Brunauer-Emmett and Teller (BET) technique. Scanning electron microscope (SEM) images show that the particles have nanoneedle-like morphology. The magnetic property is studied by vibrating sample magnetometer (VSM) technique which confirms the superparamagnetic behavior. This paper presents a simple and easy method for synthesis of magnetite/hydroxyapatite composites materials.

Keywords: iron oxide nano needles, hydroxyapatite, superparamagnetic, hyperthermia

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Authors: Asmaa Sokrat, Aykut Karaman

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Public and private spaces are major components of the morphology of the city. This research aims to study the interactions between public and private domains in terms of urban space in Casablanca. The research focuses on a general vision of a socio-spatial issue. It plans to identify the public, private, and transition (semi-public, semi-private) spaces as the constituent of the urban space. Moreover, the study investigates the link between public and private spaces with the social dimensions. Additionally, the research argues that the public space is a place of social interaction; as a reflection, this interaction is the intersection between urban space and social connectedness. Besides, social interaction can be the key to distinguishing between the public and private spheres. The methodological approach of the research is based on the literature review and field study. The article is targeting a case study on the old Medina of Casablanca, from daily use of the public and private spaces, the urban tissue, and the urban space types. In conclusion, the research exhibits that a public space could influence the privacy of the residents of a local urban area; thus, this privacy is inverted on the social interaction. This social interaction is the link between the urban space and social connectedness. Hence, this equation affects the typology of the private space.

Keywords: public sphere, private sphere, social connectedness, old Medina of Casablanca

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Authors: Neslihan Taskale Karatug, Mustafa Akcelik

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Some literature data show that misL protein play a role on host immune response formed against Salmonella Typhimurium. The aim of the present study is to learn the role of the protein in S. Typhimurium pathogenicity. To describe certain functions of the protein, primarily recombinant misL protein was produced and purified. PCR was performed using a primer set targeted to passenger domain of the misL gene on S. Typhimurium LT2 genome. Amplicon and pet28a vector were enzymatically cleaved with EcoRI and NheI. The digested DNA materials were purified with High Pure PCR Product Purification Kit. The ligation reaction was achieved with the pure products. After preparation of competent Escherichia coli Dh5α, ligation mix was transformed into the cell by electroporation. To confirm the existence of insert gene, recombinant plasmid DNA of Dh5α was isolated with high pure plasmid DNA kit. Proved the correctness of recombinant plasmid was electroporated to BL21. The cell was induced by IPTG. After induction, the presence of recombinant protein was checked by SDS-PAGE. The recombinant misL protein was purified using HisPur Ni-NTA spin colon. The pure protein was shown by SDS-PAGE and western blot immünoassay. The concentration of the protein was measured BCA Protein Assay kit. In the wake of ligation with digested products (2 kb misL and 5.4 kb pet28a) visualised on gel size of the band was about 7.4 kb and was named as pNT01. The pNT01 recombinant plasmid was transformed into Dh5α and colonies were chosen in selective medium. Plasmid DNA isolation from them was carried out. PCR was achieved on the pNT01 to check misL and 2 kb band was observed on the agarose gel. After electroporation of the plasmid and induction of the cell, 68 kDa misL protein was seen. Subsequent to the purification of the protein, only a band was observed on SDS-PAGE. Association of the pure protein with anti-his antibody was verified by the western blot assay. The concentration of the pure misL protein was determined as 345 μg/mL. Production of polyclonal antibody will be achieved by using the obtained pure recombinant misL protein as next step. The role of the protein will come out on the immune system together some assays.

Keywords: cloning, Escherichia coli, recombinant protein purification, Salmonella Typhimurium

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Authors: Wen-Yu Chen, Chia-Yuan Hsu, Sasinee Vongsrikul

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The present study is to explore the perception of Taiwanese females towards medical tourism in Thailand for the development of applicable marketing strategy, integrating travel motivation and cosmetic surgery trend to attract potential medical tourists from Taiwan. Since previous studies relevant to this research issue are limited, qualitative study is firstly employed by using one focus group interview and in-depth interviews with Taiwanese females. Moreover, the present research collected questionnaires from 290 Taiwanese females to provide greater understanding of research results. The top three factors that affect Taiwanese females’ decision for not going to Thailand for medical tourism are “physicians and nurses cannot speak Chinese”, “low quality of the cosmetic surgery product that I want to do”, and “the county does not have laws to protect medical tourists’ right”. The finding of the empirical part would suggest the area in medical tourism industry which Thailand should promote and emphasizes in order to increase its presence as a hub for cosmetic surgery and attract Taiwanese female market. Therefore, the study contributes to the potential development of marketing strategy for medical tourism, specifically in the area of cosmetic surgery in Thailand while targeting Taiwan market.

Keywords: Thailand, Taiwanese female tourists, medical tourism, cosmetic surgery

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Authors: Hiroyuki Aoki

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Molecular imaging has attracted much attention recently, which visualizes biological molecules, cells, tissue, and so on. Among various in vivo imaging techniques, the fluorescence imaging method has been widely employed as a useful modality for small animals in pre-clinical researches. However, the higher signal intensity is needed for highly sensitive in vivo imaging. The objective of the current study is the development of a fluorescent imaging agent with high brightness for the tumor imaging of a mouse. The strategy to enhance the fluorescence signal of a bio-imaging agent is the increase of the absorption of the excitation light and the fluorescence conversion efficiency. We developed a nano-particle fluorescence imaging agent consisting of a π-conjugated polymer emitting a fluorescence signal in a near infrared region. A large absorption coefficient and high emission intensity at a near infrared optical window for biological tissue enabled highly sensitive in vivo imaging with a tumor-targeting ability by an EPR (enhanced permeation and retention) effect. The signal intensity from the π-conjugated fluorescence imaging agent is larger by two orders of magnitude compared to a quantum dot, which has been known as the brightest imaging agent. The π-conjugated polymer nano-particle would be a promising candidate in the in vivo imaging of small animals.

Keywords: fluorescence, conjugated polymer, in vivo imaging, nano-particle, near-infrared

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Authors: Tanushree Jaitly, Shailendra Gupta, Leila Taher, Gerold Schuler, Julio Vera

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Genomics-based personalized medicine is a promising approach to fight aggressive tumors based on patient's specific tumor mutation and expression profiles. A remarkable case is, dendritic cell-based immunotherapy, in which tumor epitopes targeting patient's specific mutations are used to design a vaccine that helps in stimulating cytotoxic T cell mediated anticancer immunity. Here we present a computational pipeline for epitope-based personalized cancer vaccines using patient-specific haplotype and cancer mutation profiles. In the workflow proposed, we analyze Whole Exome Sequencing and RNA Sequencing patient data to detect patient-specific mutations and their expression level. Epitopes including the tumor mutations are computationally predicted using patient's haplotype and filtered based on their expression level, binding affinity, and immunogenicity. We calculate binding energy for each filtered major histocompatibility complex (MHC)-peptide complex using docking studies, and use this feature to select good epitope candidates further.

Keywords: cancer immunotherapy, epitope prediction, NGS data, personalized medicine

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Authors: R. Reshma srilakshmi, S. Shalini, P. Yogeeswari, D. Sriram

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Lysine aminotransferase is a crucial enzyme for dormancy in M. tuberculosis. It is involved in persistence and antibiotic resistance. In present work, we attempted to develop benzthiazole derivatives as lysine aminotransferase inhibitors. In our attempts, we also unexpectedly arrived at an interesting compound 21 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)benzoic acid which even though has moderate activity against persistent phase of mycobacterium, it has significant potency against active phase. In the entire series compound 22 (E)-4-(5-(2-(benzo[d]thiazol-2-yl)-2-cyanovinyl)thiophen-2-yl)isophthalic acid emerged as potent molecule with LAT IC50 of 2.62 µM. It has a significant log reduction of 2.9 and 2.3 fold against nutrient starved and biofilm forming mycobacteria. It was found to be inactive in MABA assay and M.marinum induced zebra fish model. It is also devoid of cytotoxicity. Compound 22 was also found to possess bactericidal effect which is independent of concentration and time. It was found to be effective in combination with Rifampicin in 3D granuloma model. The results are very encouraging as the hit molecule shows activity against active as well as persistent forms of tuberculosis. The identified hit needs further more pharmacokinetic and dynamic screening for development as new drug candidate.

Keywords: benzothiazole, latent tuberculosis, LAT, nutrient starvation

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Authors: Sena Park

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Background: The concurrent presentation with colorectal cancer in the inguinal hernia has been extremely rare. Due to its rarity, its presentation may lead to diagnostic and therapeutic dilemmas. We aim to review all the reported cases on colorectal cancer incarcerated in the inguinal hernia in the last 20 years, and discuss the operative approaches. Methods: We identified all case reports on colorectal cancer within inguinal hernia using PUBMED (2002-2022) and MEDLINE (2002-2022). The search strategy included the following keywords: colorectal cancer (title/abstract) AND inguinal hernia (title/abstract) OR incarceration (title/abstract). The search did not include letters, book chapters, systemic reviews, meta-analysis and editorials. Results: In the last 20 years, a total of 19 cases on colorectal cancer within the inguinal hernia were identified. The age of the patients ranged between 48 and 89. Majority of the patients were male (95%). Most commonly involved part of the large intestine was sigmoid colon (79%). Of all the cases, 79 percent of patients received open procedure and 21 percent had laparoscopic procedure. Discussion: Inguinal hernias are common with an incidence of approximately 1.7 percent. Colorectal cancer is the one of the leading causes of cancer-related mortality worldwide. However, their concurrent presentation has been extremely rare. In the last 20 years, 19 cases on concurrent presentation of colorectal cancer and inguinal hernia have been reported. Most patients who had open procedures had two incisions of groin incision and a midline laparotomy. There were 4 cases where the oncological resection was performed laparoscopically. The advantages of laparoscopic resection include reduced blood lost, reduced post-operative pain, reduced length of hospital stay and similar number of lymph nodes taken. From the review of the cases in the last 20 years, both open and laparoscopic approaches seemed to be safe and achieve adequate oncological resections. Conclusion: This is a brief overview of reported cases of colorectal cancer presenting with inguinal hernia concurrently. Due to its rarity, there are no current guidelines on operative approach in clinical practice. The experience in the last 20 years supports both open and laparoscopic approach.

Keywords: colorectal cancer, inguinal hernia, incarceration, operative approach

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Authors: Jingyuan Hu, Zhandong Liu

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CRISPR genome editing technology has transformed molecular biology by accurately targeting and altering an organism’s DNA. Despite the state-of-art precision of CRISPR genome editing, the imprecise mutation outcome and off-target effects present considerable risk, potentially leading to unintended genetic changes. Targeted deep sequencing, combined with bioinformatics sequence alignment, can detect such unwanted mutations. Nevertheless, the classical method, Needleman-Wunsch (NW) algorithm may produce false alignment outcomes, resulting in inaccurate mutation identification. The key to precisely identifying CRISPR-induced mutations lies in determining optimal parameters for the sequence alignment algorithm. Hidden Markov models (HMM) are ideally suited for this task, offering flexibility across CRISPR systems by leveraging forward-backward algorithms for parameter estimation. In this study, we introduce CRISPR-HMM, a statistical software to precisely call CRISPR-induced mutations. We demonstrate that the software significantly improves precision in identifying CRISPR-induced mutations compared to NW-based alignment, thereby enhancing the overall understanding of the CRISPR gene-editing process.

Keywords: CRISPR, HMM, sequence alignment, gene editing

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Authors: Mina Mortazavi, Pezhman Sharafi

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Cold-formed steel sections are popular construction materials as structural or non-structural elements. The objective of this paper is to propose an optimisation method for open cross sections targeting the maximum nominal axial strength. The cross sections considered in the optimisation process should all meet a determined critical global buckling load to be considered as a candidate for optimisation process. The maximum dimensions of the cross section are fixed and limited into a predefined rectangular area. The optimisation process is repeated for different available coil thicknesses of 1 mm, 2.5 mm and 3 mm to determine the optimum thickness according to the cross section buckling behaviour. A simple-simple boundary is assumed as end conditions. The number of folds is limited to 20 folds to prevent extra complicated sections. The global buckling load is considered as Euler load and is determined according to the moment of inertia of the cross-section with a constant length. The critical buckling loads are obtained using Finite Strip Method. The results of the optimisation analysis are provided, and the optimum cross-section within the considered range is determined.

Keywords: shape optimisation, buckling, cold formed steel, finite strip method

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Authors: Megan E. Davies

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As substance use become an increasing prevalent occurrence amongst young people, prevention programs designed specifically for children and adolescents are required to protect against associated cognitive, psychological, and behavioural issues. Further, young people from marginalized backgrounds would highly benefit from culturally adapted substance use prevention programs. The first and second phase of the Life Skills Training (LST) program, the Maskwacis Life Skills Training (MLST) program, the Bii-Zin-Da-De-Da (BZDDD; “Listening to One Another”), and a culturally sensitive smoking prevention program, all of which have been adapted to Canadian Indigenous cultures and are applied within the school and family settings, are discussed. Additionally, comorbid disorders, at-risk personality types, and motivating factors associated with substance use amongst Canadian children and adolescents, specifically Indigenous youth, are explored through the application of a biopsychosocial model. Requital efforts being made in Canada towards Indigenous communities are described within a historical context, and substance use prevention programs targeting Indigenous children and adolescents are compared. Through this lens, suggestions are presented for future research on preventative interventions directed towards substance use within minority groups.

Keywords: early intervention, cultural appropriateness, life skills training, smoking prevention, drug and alcohol prevention

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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NASH is an increasingly prevalent chronic liver disease that can progress to hepatocellular carcinoma and now is attracting interest worldwide. The STAM™ model is a clinically-correlated murine NASH model which shows the same pathological progression as NASH patients and has been widely used for pharmacological and basic research. The multiple parallel hits hypothesis suggests abnormalities in adipocytokines, intestinal microflora, and endotoxins are intertwined and could contribute to the development of NASH. In fact, NASH patients often exhibit gut dysbiosis and dysfunction in adipose tissue and metabolism. However, the analysis of the STAM™ model has only focused on the liver. To clarify whether the STAM™ model can also mimic multiple pathways of NASH progression, we analyzed the organ crosstalk interactions between the liver and the gut and the phenotype of adipose tissue in the STAM™ model. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin 2 days after birth and feeding with high-fat diet after 4 weeks of age. The mice were sacrificed at NASH stage. Colon samples were snap-frozen in liquid nitrogen and stored at -80˚C for tight junction-related protein analysis. Adipose tissue was prepared into paraffin blocks for HE staining. Blood adiponectin was analyzed to confirm changes in the adipocytokine profile. Tight junction-related proteins in the intestine showed that expression of ZO-1 decreased with the progression of the disease. Increased expression of endotoxin in the blood and decreased expression of Adiponectin were also observed. HE staining revealed hypertrophy of adipocytes. Decreased expression of ZO-1 in the intestine of STAM™ mice suggests the occurrence of leaky gut, and abnormalities in adipocytokine secretion were also observed. Together with the liver, phenotypes in these organs are highly similar to human NASH patients and might be involved in the pathogenesis of NASH.

Keywords: Non-alcoholic steatohepatitis, hepatocellular carcinoma, fibrosis, organ crosstalk, leaky gut

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Authors: Shaker Alsharif, Xavier Banquy

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Controlled drug delivery technology represents one of the most rapidly advancing areas of science in which chemists and chemical engineers are contributing to human health care. Such delivery systems provide numerous advantages compared to conventional dosage forms including improved efficacy, and improved patient compliance and convenience. Such systems often use synthetic polymers as carriers for the drugs. As a result, treatments that would not otherwise be possible are now in conventional use. The role of bilayered vesicles as efficient carriers for drugs, vaccines, diagnostic agents and other bioactive agents have led to a rapid advancement in the liposomal drug delivery system. Moreover, the site avoidance and site-specific drug targeting therapy could be achieved by formulating a liposomal product, so as to reduce the cytotoxicity of many potent therapeutic agents. Our project focuses on developing and building hydrogel with nanoinclusion of liposomes loaded with active compounds such as proteins and growth factors able to release them in a controlled fashion. In order to achieve that, we synthesize several liposomes of two different phospholipids concentrations encapsulating model drug. Then, formulating hydrogel with specific mechanical properties embedding the liposomes to manage the release of active compound.

Keywords: controlled release, hydrogel, liposomes, active compounds

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Authors: Reem Al-Shidhani, Isabelle S. R. Storer, Michael J. Bromley, Lydia Tabernero

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Invasive fungal diseases are an increasing global health concern that contributes to the high mortality rates in immunocompromised patients. The rising of antifungal resistance severely lowers the efficacy of the limited antifungal agents available. New antifungal drugs that target new mechanisms are necessary to tackle the current shortfalls. Amongst post- modifications, phosphorylation is a predominant and an outstanding protein alteration in all eukaryotes. In fungi, protein phosphorylation plays a vital role in many signal transduction pathways, including cell cycle, cell growth, metabolism, transcription, differentiation, proliferation, and virulence. The investigation of Aspergillus fumigatus phosphatases revealed seven genes essential for viability. Inhibiting one of these phosphatases is a new interesting route to develop novel antifungal drugs. In this study, we carried out an early drug discovery process targeting oneessential phosphatase, GlcA. Here, we report the identification of new GlcA inhibitors that show antifungal activity. These important finding open a new avenue to the development of novel antifungals to expand the current narrow arsenal of clinical candidates.

Keywords: invasive fungal diseases, phosphatases, GlcA, competitive inhibitors

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Authors: Rehana Akhter, Sajad A. Rather, F. A. Masoodi, Adil Gani, S. M. Wani

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During recent years probiotic food products receive market interest as health-promoting, functional foods, which are believed to contribute health benefits. In order to deliver the health benefits by probiotic bacteria, it has been recommended that they must be present at a minimum level of 106 CFU/g to 107 CFU/g at point of delivery or be eaten in sufficient amounts to yield a daily intake of 108 CFU. However a major challenge in relation to the application of probiotic cultures in food matrix is the maintenance of viability during processing which might lead to important losses in viability as probiotic cultures are very often thermally labile and sensitive to acidity, oxygen or other food constituents for example, salts. In this study Lactobacillus plantarum and Lactobacillus casei were encapsulated in calcium alginate beads with the objective of enhancing their survivability and preventing exposure to the adverse conditions of the gastrointestinal tract and where then inoculated in mutton nuggets. Micro encapsulated Lactobacillus plantarum and Lactobacillus casei were resistant to simulated gastric conditions (pH 2, 2h) and bile solution (3%, 2 h) resulting in significantly (p ≤ 0.05) improved survivability when compared with free cell counterparts. A high encapsulation yield was found due to the encapsulation procedure. After incubation at low pH-values, micro encapsulation yielded higher survival rates compared to non-encapsulated probiotic cells. The viable cell numbers of encapsulated Lactobacillus plantarum and Lactobacillus casei were 107-108 CFU/g higher compared to free cells after 90 min incubation at pH 2.5. The viable encapsulated cells were inoculated into mutton nuggets at the rate of 108 to 1010 CFU/g. The micro encapsulated Lactobacillus plantarum and Lactobacillus casei achieved higher survival counts (105-107 CFU/g) than the free cell counterparts (102-104 CFU/g). Thus micro encapsulation offers an effective means of delivery of viable probiotic bacterial cells to the colon and maintaining their survival during simulated gastric, intestinal juice and processing conditions during nugget preparation.

Keywords: survival, Lactobacillus plantarum, Lactobacillus casei, micro-encapsulation, nugget

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Authors: Manuela Amorim, Cláudia S. Marques, Maria Conceição Calhau, Hélder J. Pinheiro, Maria Manuela Pintado

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Recently it has been recognized peptides from different food sources with biological activities. However, no relevant study has proven the potential of brewer yeast peptides in the modulation of gut microbiota. The importance of human intestinal microbiota in maintaining host health is well known. Probiotics, prebiotics and the combination of these two components, can contribute to support an adequate balance of the bacterial population in the human large intestine. The survival of many bacterial species inhabiting the large bowel depends essentially on the substrates made available to them, most of which come directly from the diet. Some of these substrates can be selectively considered as prebiotics, which are food ingredients that can stimulate beneficial bacteria such as Lactobacilli or Bifidobacteria growth in the colon. Moreover, conventional food can be used as vehicle to intake bioactive compounds that provide those health benefits and increase people well-being. In this way, the main objective of this work was to study the potential prebiotic activity of brewer yeast peptide extract (BYP) obtained via hydrolysis of yeast proteins by cardosins present in Cynara cardunculus extract for possible use as a functional ingredient. To evaluate the effect of BYP on the modulation of gut microbiota in diet-induced obesity model, Wistar rats were fed either with a standard or a high-fat diet. Quantified via 16S ribosomal RNA (rRNA) expression by quantitative PCR (qPCR), genera of beneficial bacteria (Lactobacillus spp. and Bifidobacterium spp.) and three main phyla (Firmicutes, Bacteroidetes and Actinobacteria) were assessed. Results showed relative abundance of Lactobacillus spp., Bifidobacterium spp. and Bacteroidetes was significantly increased (P < 0.05) by BYP. Consequently, the potential health-promoting effects of WPE through modulation of gut microbiota were demonstrated in vivo. Altogether, these findings highlight the possible intervention of BYP as gut microbiota enhancer, promoting healthy life style, and the incorporation in new food products, leads them bringing associated benefits endorsing a new trend in the improvement of new value-added food products.

Keywords: functional ingredients, gut microbiota, prebiotics, brewer yeast peptide extract

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Authors: Jovana Bogojeski, Dusan Cocic, Nenad Jankovic, Angelina Petrovic

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Kinetically-inert transition metal complexes, such as Rh(III) and Os(III) complexes, attract increasing attention as leading scaffolds for the development of potential pharmacological agents due to their inertness and stability. Therefore, we have designed and fully characterized a few novel rhodium(III) and osmium(III) complexes with a tridentate nitrogen−donor chelate system. For some complexes, the crystal X-ray structure analysis was performed. Reactivity of the newly synthesized complexes towards small biomolecules, such as L-methionine (L-Met), guanosine-5’-monophosphate (5’-GMP), and glutathione (GSH) has been examined. Also, the reactivity of these complexes towards the DNA/RNA (Ribonucleic acid) duplexes was investigated. Obtained results show that the newly synthesized complexes exhibit good affinity towards the studied ligands. Results also show that the complexes react faster with the RNA duplex than with the DNA and that in the DNA duplex reaction is faster with 15mer GG than with the 22mer GG. The UV-Vis (Ultraviolet-visible spectroscopy) is absorption spectroscopy, and the EB (Ethidium bromide) displacement studies were used to examine the interaction of these complexes with CT-DNA and BSA (Bovine serum albumin). All studied complex showed good interaction ability with both the DNA and BSA. Furthermore, the DFT (Density-functional theory) calculation and docking studies were performed. The impact of the metal complex on the cytotoxicity was tested by MTT assay (a colorimetric assay for assessing cell metabolic activity) on HCT-116 lines (human colon cancer cell line). In addition, all these tests were repeated in the presence of several water-soluble biologically active ionic liquids. Attained results indicate that the ionic liquids increase the activity of the investigated complexes. All obtained results in this study imply that the introduction of different spectator ligand can be used to improve the reactivity of rhodium(III) and osmium(III) complexes. Finally, these results indicate that the examined complexes show reactivity characteristics needed for potential anti-tumor agents, with possible targets being both the DNA and proteins. Every new contribution in this field is highly warranted due to the current lack of clinically used Metallo-based alternatives to cisplatin.

Keywords: biomolecules, ionic liquids, osmium(III), rhodium(III)

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Authors: Seunghwan Seo, Woo-Seok Lee, Ji-Sun Shin, Young Kyoung Rhee, Chang-Won Cho, Hee-Do Hong, Kyung-Tae Lee

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Doenjang, known as traditional Korean food, is product of a natural mixed fermentation process carried out by lactic acid bacteria (LAB). Lactobacillus sakei K040706 (K040706) has been accepted as the most populous LAB in over ripened doenjang. Recently, we reported the immunostimulatory effects of K040706 in RAW 264.7 macrophages and in a cyclophosphamide-induced mouse model. In this study, we investigated the ameliorative effects of K040706 in a dextran sulfate sodium (DSS)-induced colitis mouse model. We induced colitis using DSS in 5-week-ICR mice over 14 days with or without 0.1, 1 g/kg/day K040706 orally. The body weight, stool consistency, and gross bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and colonic tissues were collected and subjected to histological experiments and myeloperoxidase (MPO) accumulation, cytokine determination, qRT-PCR and Western blot analysis. Results showed that K040706 significantly attenuated DSS-induced DAI score, shortening of colon length, enlargement of spleen and immune cell infiltrations into colonic tissues. Histological examinations indicated that K040706 suppressed edema, mucosal damage, and the loss of crypts induced by DSS. These results were correlated with the restoration of tight junction protein expression, such as, ZO-1 and occludin in K040706-treated mice. Moreover, K040706 reduced the abnormal secretions and mRNA expressions of pro-inflammatory mediators, such as nitric oxide (NO), tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). DSS-induced mRNA expression of intercellular adhesion molecule (ICAM) and vascular cell adhesion molecule (VCAM) in colonic tissues was also downregulated by K040706 treatment. Furthermore, K040706 suppressed the protein and mRNA expression of toll-like receptor 4 (TLR4) and phosphorylation of NF-κB and signal transducer and activator of transcription 3 (STAT3). These results suggest that K040706 has an anti-colitic effect by inhibition of intestinal inflammatory responses in DSS-induced colitic mice.

Keywords: Lactobacillus sakei, NF-κB, STAT3, ulcerative colitis

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Authors: Nini Johana Marin Rodriguez

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This paper applies DCC, EWMA and OGARCH models to compare the dynamic correlations between exchange rates, oil prices, exchange rates and stock markets to examine the time-varying conditional correlations to the daily oil prices and index returns in relation to the US dollar/local currency for developed (Canada and Mexico) and emerging Latin American markets (Brazil, Chile, Colombia and Peru). Changes in correlation interactions are indicative of structural changes in market linkages with implications to contagion and interdependence. For each pair of stock price-exchange rate and oil price-US dollar/local currency, empirical evidence confirms of a strengthening negative correlation in the last decade. Methodologies suggest only two events have significatively impact in the countries analyzed: global financial crisis and Europe crisis, both events are associated with shifts of correlations to stronger negative level for most of the pairs analyzed. While, the first event has a shifting effect on mainly emerging members, the latter affects developed members. The identification of these relationships provides benefits in risk diversification and inflation targeting.

Keywords: crude oil, dynamic conditional correlation, exchange rates, interdependence, stock prices

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Authors: Qiang Xu, Xingxin Wu, Wenjie Guo, Xingqi Wang, Yang Sun, Renxiang Tan

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The phosphatase SHP-2 is known to exert regulatory activities on cytokine receptor signaling and the dysregulation of SHP-2 has been implicated in the pathogenesis of a variety of diseases. Here we report several small molecule regulators of SHP-2 for the treatment of T cell-mediated diseases. The new cyclodepsipeptide trichomides A, isolated from the fermentation products of Trichothecium roseum, increased the phosphorylation of SHP-2 in activated T cells, and ameliorated contact dermatitis in mice. The trichomides A’s effects were significantly reversed by using the SHP-2-specific inhibitor PHPS1 or T cell-conditional SHP-2 knockout mice. Another compound is a cerebroside Fusaruside isolated from the endophytic fungus Fusarium sp. IFB-121. Fusaruside also triggered the tyrosine phosphorylation of SHP-2, which provided a possible mean of selectively targeting STAT1 for the treatment of Th1 cell-mediated inflammation and led to the discovery of the non-phosphatase-like function of SHP-2. Namely, the Fusaruside-activated pY-SHP-2 selectively sequestrated the cytosolic STAT1 to prevent its recruitment to IFN-R, which contributed to the improvement of experimental colitis in mice. Blocking the pY-SHP-2-STAT1 interaction, with SHP-2 inhibitor NSC-87877 or using T cells from conditional SHP-2 knockout mice, reversed the effects of fusaruside. Furthermore, the fusaruside’s effect is independent of the phosphatase activity of SHP-2, demonstrating a novel role for SHP-2 in regulating STAT1 signaling and Th1-type immune responses.

Keywords: SHP-2, small molecules, T cell, T cell-mediated diseases

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Authors: Raana Babadi Fathipour

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Ice cream is a nutritious dairy product that, given its constituent materials and high nutritional value, is a suitable growth medium for the growth of various food microorganisms. The contamination of this product with pathogenic microorganisms may cause food poisoning and infections, and so could be harmful to human health. The foremost critical pathogenic microscopic organisms of ice cream incorporate Escherichia coli, Staphylococcus aureus, Bacillus cereus, Enterobacteriaceae, coliforms, Listeria monocytogenes and Enterococcus. Biosensor technology, albeit a recent addition to the dairy industry, has proven its worth in other fields, such as medical devices. Through numerous studies, the advantages of employing biosensors have consistently emerged. These incredible tools present expeditious and straightforward means while specifically targeting analytes. Thus, they bring forth unparalleled solutions that bolster ongoing advancements within dairy products and processes. This review delves into the latest developments in the realm of biosensors and evaluates the diverse techniques of bio-recognition and transduction in terms of their benefits, drawbacks, and relevance to traditional ice cream. Furthermore, the obstacles that impede the progress of these approaches in meeting the growing need for swift and real-time quality control of milk products, particularly ice cream, are also expounded upon.

Keywords: traditional ice cream, Escherichia coli, Staphylococcus aureus, biosensors

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