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An inaugural editorial sets scope and standards for the journal, highlighting emerging areas in chemical methods, materials, and interfaces with biology and energy.
Breathing has long been recognised as a vital process in Eastern traditions such as YOGA and Ayurvedic medicine, where Pranayama is regarded as a transformative practice that harmonises body and mind. While the East developed sophisticated systems of breath regulation for health and self-awareness, the West largely overlooked their significance until the late 19th and early 20th centuries. A group of pioneering physicians, sometimes referred to as "the pulmonauts", including Christian Bohr, Konstantin Buteyko, and Peter M Litchfield, explored the physiological foundations of respiration. They emphasised the benefits of slow, nasal breathing and its relationship to both physical and emotional well- being. In the 21st century, contemporary researchers and practitioners such as James Nestor, J. Patrick McKeown and Anders Olsson have expanded this understanding through the fields of biochemistry, physiology, and biomechanics. Their work has clarified the mechanisms underlying conscious breathing and refined ancient pranayama techniques. Integrating insights from both Eastern and Western traditions reveals that breathing is a central factor in maintaining homeostasis and emotional balance.
The body interacts with endogenous and exogenous molecules through various receptor networks at the cellular and organismal levels by which the different physiological processes of the organ systems get activated. Life could no longer exist without the body’s interaction with these signaling molecules. The number of molecules interacted with a receptor type within the body determines the efficiency of biological processes that would determine the biochemistry and anatomy behind the basic body functions. The dose plays a complex role in multiple physiological processes by modulating the natural processes of the different biological systems. It is always connected to the physiological and anatomical aspects of the biological sciences in which it manifests the biological sensitivity that would determine the efficiency of biological responses of the body systems. There are always physiologic and non-physiologic doses for every compound administered into the biological systems. The does that facilitated the body to manifest that biological sensitivity which has maintained the physiological processes of the body systems was noted as physiologic dose, whereas the dose that has suppressed the biological sensitivity of the body that became inefficient in maintaining the physiological processes of the different biological systems was termed non-physiologic dose. It is important to adjust the dose or dosage based on physical and biological factors such as the efficiency of the different organ systems, body weight, and the timing of the dose triggering a biological response to maintain the natural processes of the body systems. This means that integrated biological data is required in order to be able to identify the physiologic and non physiologic doses for biological or pharmacological use.
Significance This case report describes the alternative management of hyperuricemia through acupuncture using the Luo Yuan technique. Case presentation A 53-year-old Mexican man was diagnosed with secondary hyperuricemia. The patient began to experience arthralgia in the metatarsophalangeal joint of the first toe on his left foot after consuming a high amount of purine-rich foods, with a 10-year history. The symptoms were sporadically controlled with the use of colchicine and indarzone. In a six-element blood chemistry test, serum uric acid was 8.7 mg/dL before acupuncture treatment and 8.3 mg/dL at the end of treatment, without applying dietary restrictions on purine consumption. Conclusions and relevance This report demonstrates the potential efficacy of acupuncture at the Luo and Yuan points of the Spleen and Stomach meridians in reducing elevated blood uric acid levels. This suggests its potential as an alternative treatment for patients with hyperuricemia and other metabolic disorders.
Introduction Angiosarcoma is a rare malignant tumour from fast-evolving and aggressive vascular endothelial cells that accounts for 1% of all sarcomas. The sinus location of angiosarcoma is exceptional. The clinical polymorphism of this tumour may cause a delay in diagnosis. Risk factors are not always understood. However, a history of radiation therapy for locoregional cancer and/or lymphedema is most commonly found. The prognosis remains bleak with an overall five-year survival of 35 to 40%. Objectives The authors discuss the diagnostic, therapeutic and prognostic modalities and difficulties of this tumour. Observation: The authors report a case of maxillary sinus angiosarcoma confirmed by radio-induced secondary CD34 immunohistological staining in a 40-year-old man having a history of hemangioendothelioma treated with conservative endoscopic surgery and adjuvant radiotherapy 15 months earlier. Discussion This lesion is rare in the ENT sphere and may be confused with a benign tumor in its early stages. Only histological examination with immunohistochemistry can confirm the diagnosis (factor VIII, CD34 and CD31 antigens). Treatment consists of a wide resection followed by radiotherapy, hence the need for early diagnosis in the metastatic phase, first-line treatments include doxorubicin or paclitaxel weekly. Conclusion Radio-induced angiosarcoma is a rare malignant tumour, it occurs in patients who have received conservative treatment and radiation therapy for nasosinusitis cancers. Angiosarcomas of the nasal passages remain a diagnostic and therapeutic challenge due to their local and general aggressiveness.
One of the primary goals and aims of studying chemistry in society is the promotion of the well-being of humanity and the sustainable utilization of the available resources. Chemistry has played a significant role in water treatment, food production, energy production, and medicine, among other critical areas of society. This study explored the utilization of liquid chromatography-mass spectrometry in the aspect of promoting food safety for human consumption. Various factors might affect the composition and storage of the food items in the society. Through the utilization of chemistry techniques such as (LC-MS), there can be Identification of the various aspects that require consideration in the Improvement of the different health and nutritional requirements that the food items are expected to have in society. As illustrated in this study, the analytical and technical aspects are highly influential in the determination of the proper measures for each component and the illustration of the various toxins that are likely to affect the overall food safety of the members of society in general.
Steroid cell tumors of the ovary are particularly rare, secreting sex hormones, characterized by steroid cell proliferation and represent only 0.1% of all ovarian tumors. They are classified into three subtypes according to their cell of origin: stromal luteoma, Leydig cell tumors and a third subtype of unknown lineage corresponds to a not specified steroid cell tumor (SCT-NOS). This third subtype accounts for 60% of steroid cell tumors. The clinical manifestations of SCT-NOS can take many forms, including pain, abdominal distension, but perhaps the most visible presentations are those related to hormonal activity and virilization of the tumor. We present a rare case of a 48-year-old woman with vaginal bleeding and a history of trunk obesity, hirsutism for 2 years and hypothyroidism with hormone replacement therapy. Clinical examination revealed a characteristic of obesity, virilization. Serum testosterone was 3.62 µg / L and CA-125 was 40.67. Magnetic resonance imaging identified a left ovarian solid mass and histopathology confirmed a steroid cell tumor not specific. The patient underwent exploratory laparotomy and left salpingoophorectomy. Macroscopically, the mass is well circumscribed, solid, homogeneous and yellowish. Microscopically, the tumor is mainly composed of eosinophilic or vacuolar granular cytoplasm. Immunohistochemistry showed that the tumor cells were strongly positive for inhibin. The postoperative period was uneventful. Through this rare observation, we will discuss the aspects that characterize this type of tumor and present some guidelines to be used in the differential diagnosis, as well as the difficulties encountered in the clinical, radiological and therapeutic fields.
Background Human malignant cell models which reflect the structural and physiological complexity of tumor tissue are of great importance for preclinical research in oncology. Spheroids/tumoroids derived from solid tumors are of great interest as cellular models mimicking the first vascular-free growth phase of a tumor node. The fact of the identity between artificially created tumor multicellular aggregates and the real tumor tissue, however, needs to be specified, described and validated in order to see how closely the spheroids are biologically similar to the malignized tissues in vivo compared to the monolayer cell cultures traditionally used. We present here a comparison study of the characteristics of solid tumor cells of different histogenesis (melanomas, soft tissue sarcomas and bone sarcomas, epithelial tumors) cultured in two dimensions (monolayer culture) and three dimensional space (spheroid), namely: spatial organization, multiplication, metabolic activity. Patients and Methods For the creation of 2 D and 3D cell models the cells isolated from the patient's solid tumor fragments obtained intraoperatively were used. 15 samples of skin melanoma, 20 samples of soft tissue and osteogenic sarcomas (STBS), and 9 samples of epithelial tumors (ET). The tumor cells were all cultivated for at least 10 passages. We used phase contrast, confocal microscopy, and immunohistochemistry to investigate spheroids and monolayer cultures. The supernatants of tumor cells grown in 2D and 3D cultures were studied using ELISA and multiplex analysis for the production of a spectrum of chemokines and cytokines supporting the immunosuppression, invasion and metastasis processes. Results Tumor specimens received were predominantly of metastatic origin (75%). In 100% of cases 2D cultures were received, in 88.6% of cases (39 out of 44) we succeeded in obtaining spheroids. There was no direct correlation between the efficiency of tumoroid formation and the tumor's histogenetic origin and the stage of the cancer process (primary tumor, recurrence, metastasis). The median size of spheroids by 4-5 days of cultivation with a starting concentration of 10000 cells per well was 657.14 μm for melanoma (min 400 - max 1000 μm), 571.42 μm (min 400 - max 700 μm), 507.14 μm (min 300 - max 600 μm) for soft tissue sarcomas, 650.0 μm (min 400 - max 900 μm) for osteogenic sarcomas. Immunochemical analysis of Ki-67, GLUT1, and Ecadherin markers was carried out for tumor tissue samples, single-layer tumor cultures, and tumoroids of every patient. The distribution of the stained groups in the spheroids was distinct from the monolayer cultures and more in accordance with the distribution of such in the tissue tumor, the number of Ki-67+ cells was increasing in the spheroids. We detected no dependence of Ki-67+ and GLUT1+ cell localization grade on spheroid size. We identified E-cadherin in tumor tissue and tumoroids of breast carcinoma and one melanoma culture. Monolayer cultures did not express it. The increase in secretory cell activity of the solid tumor cells from 2D to 3D system was observed when CCL2, CCL3, CXCL1, CXCL16, MIF, IL10, MICA (p<0.01) were investigated. Conclusion The presence of patient-specific cells of solid tumors in a 3D environment causes activation of the proliferative and metabolic processes as compared to monolayer cultures, which makes these models approximate the real world clinical picture. The production of chemokines that can attract to the tumor various types of immune system cells, to include their immature versions, as well as production of cytokines and Immunosuppression factors that, when present in the tumor microenvironment in the high concentrations, contribute to the formation of immune cells having suppressive capacities occurs in the 3D cell system. Three-dimensional model of the initial tumor nodule formation stage thus demonstrates the forming process of tumor cells favorable for them microenvironment. Construction of three-dimensional models - spheroids of tumor cells of differing histogenesis demands individual approach and more thorough investigation.
The aim of the study was to evaluate the immunomodulatory activity of the Biofield Treated/Blessed proprietary test formulation consisting of essential ingredients viz. minerals (zinc, magnesium, iron, and copper) and vitamins (B6, B12, and D3) in male Sprague Dawley rats. Each ingredient of the test formulation was divided into two parts. One part was denoted as the control without any Biofield Energy Healing Treatment/Blessing, while the other part was defined as the Biofield Energy Treated/Blessed sample, which received the Biofield Energy Healing Treatment/Blessing by a renowned Biofield Energy Healer, Mr. Mahendra Kumar Trivedi remotely. Additionally, three group of animals were also received Biofield Energy Treatment per se (at day -15) under similar conditions. The parameters were assessed such as immune biomarkers (IgM, IgG, IgA, IgE, CD4+, CD8+, and CD28+), biochemistry and hematology and histopathology. The experimental results showed IgG level was significantly increased by 10.70% and 8.03% in the G6 (Biofield Energy Treatment per se at day -15) and G8 (Biofield Treatment per se to animals plus Biofield Treated test formulation from day -15) groups, respectively as compared with untreated test formulation (G4). Additionally, CD8+ count was significantly increased by 20.67% in the G8 group, while CD28+ count was significantly increased by 11.70%, 8.32%, and 9.82% in the G7 (Biofield Energy Treated test formulation at day -15), G8, and G9 (Biofield Treatment per se (day -15) to animals plus untreated test formulation) groups, respectively after Biofield Energy Treatment to the animals as compared with the untreated test formulation. In hematological analysis, platelet count was increased in the G5, G6, G7, G8, and G9 groups by 40.69%, 27.95%, 26.67%, 38.58%, and 28.28%, respectively compared with the disease control (G2) group. Biochemical parameters showed significant decrease in the level of creatinine by 32.14% in the G9 group as compared with the G2 group. Further, animal body weight, feed intake, relative organ weight, and histopathological findings of all the tested groups did not show any abnormal findings with respect to the safe and non-toxic treatment strategies. Overall, the experimental data concluded that the Biofield Energy Treated/Blessed test formulation showed considerable improved cellular and humoral immune response as compared with the untreated test formulation. Thus, the Trivedi Effect®-Biofield Energy Healing Treatment per se and the test formulation has the significant capacity for immunomodulatory effect, stress management and anti-aging by improving overall health.
Breast implant-associated anaplastic large cell lymphoma (ALCL) is a recently recognized type of T-cell lymphoma that can develop following breast implants, with morphologic and immunophenotypic features indistinguishable from those of ALK-negative ALCL. Here we report a case of a 58-year-old woman with a history of subglandular silicone implants placed for bilateral breast augmentation 25 years ago, who presented with bilateral breast pain and was found to have bilateral Baker Grade III capsular contracture, and heterogenous fluid collection centered near the left third costochondral articulation, a suspicious left chest wall lesion, and left axillary lymphadenopathy on imaging. A left axillary lymph node core biopsy and an aspiration of the fluid were performed, and no malignant cells were identified. The patient underwent bilateral removal of breast implants and total capsulectomies. Microscopic examination of the capsule surrounding the left breast implant revealed large pleomorphic tumor cells in a fibrinous exudate. By immunohistochemistry, the tumor cells were found to be positive for CD3 (subset), CD4, CD7, CD30 (strong and uniform), and CD43, and negative for CD2, CD5, CD8, and ALK1, supporting the diagnosis of breast implant-associated ALCL. No lymphoma cells were identified in the right breast capsule, confirmed by CD30 stain. Breast implant-associated ALCL is a very rare disease that can develop many years after breast implant placement. Proper evaluation with breast imaging and pathologic workup is essential to confirm the diagnosis in suspected cases. Our case highlights that adequate sampling is important in the investigation of patients with suspected breast implant-associated ALCL.
Plasma cell neoplasms of the thyroid gland are uncommon. They may occur either as a primary extraosseous (extramedullary) plasmacytoma or as secondary involvement by multiple myeloma (MM). Here, we report the case of a 62-year-old female, presenting with goiter and Hashimoto’s thyroiditis, in whom the histologic diagnosis of extraosseous plasmacytoma was unexpected. Histology of the total thyroidectomy specimen showed a diffuse infiltration of well-differentiated plasma cells against a background of Hashimoto’s thyroiditis. By immunohistochemistry, the majority of the plasma cells are positive for IgG heavy chain and kappa light chain (kappa:lambda ratio was about 6-7:1). PCR analysis of the immunoglobulin heavy and kappa chain (IGH, IGK) gene rearrangements showed clonal IGH and IGK gene rearrangements. MM was ruled out by lack of MM-related end organ damage and negative serum protein electrophoresis, immunofixation, and bone marrow biopsy. Although rare, plasmacytoma should be considered in patients presenting with enlarging thyroid gland and autoimmune thyroiditis. Histologic diagnosis and differential diagnoses are comprehensively discussed.
The brain requires certain fuels to function in high level. Literally, nutritional components can modulate the brain productivity. One of the right nutrition to enhance the brain power is dietary component of caffeine. Caffeine as a component of coffee, tea and chocolate is very popular. Although, depending on the dietary demands or conventional habits some people do not consume caffeine-containing substances (i.e. foods or beverage). Nonetheless, caffeine constituents maximize the brain potential via promoting the central nervous system (CNS) through blocking an inhibitory neurotransmitter (adenosine) and releasing some other specific neurotransmitters (noradrenaline, dopamine and serotonin) in brain. The chemistry of caffeine in a standard dose in fact can affect the brain intelligence.
Papillary carcinoma is a mammary neoplasia of women and female dogs characterized by papillary fibrovascular projections lined by epithelial cells. Evaluation on the biology of these tumors can be done by immunohistochemistry through detection of alpha-smooth muscle actin protein in the papillary myoepithelium, which lacks such a molecule during malignant proliferations. Thus, this study aimed at determining the malignancy degree of papillary mammary tumors of female dogs by immunohistochemistry. Twenty samples of mammary neoplastic tissues collected from female dogs treated in the Veterinary Hospital at FCAV were evaluated by Hematoxylin and Eosin staining (H&E) and tumor cells were immunolabelled with monoclonal antibody to alpha-smooth muscle actin (α-SMA). Five out of 20 cases showed positive immunolabeling greater than 10% of the total immunolabeling. The remaining fourteen cases presented immunostaining lesser than 10% showing decrease or absence of α-SMA labeling in the myoepithelium of the papilla tumors. All those cases in which immunostained cell was over 10% of the neoplasm (5 immunostains of 20 total cases) were classified as benign whereas those below 10% of immunostained in the slid were considered as malignant. Therefore, immunohistochemistry played an essential role in differentiating benign and malignant papillary tumors of bitches as already described for female. Tumor classification by conventional methods, such as H&E staining, can lead to erroneous interpretations on the real biological behavior of the papillary mammary tumor.
Background Hypothyroidism is a metabolic disorder affecting the functions of many tissues in the body including the testis. Testis is rich in the polyunsaturated fatty acids content and lacks strong intrinsic antioxidant system making it prone to such oxidative stress. L-carnitine (LC) regulates long chain fatty acids metabolism; and is considered a valuable antioxidant factor. Aim It was to evaluate the effect of hypothyroidism induced by propylthiouracil (PTU) on rats’ testes and the possible protective role of LC. Methods Forty-eight adult male albino rats were used in this work. The animals were divided into three groups with sixteen animals in each. Group 1 (Control): Animals were kept without medications. Group 2 (PTU-treated): was subjected to administration of PTU; while group 3 (PTU and LC) received both PTU and LC. By the end of the experiment “30 days”, blood samples were taken for hormonal assay; then animals were anaesthetized and sacrificed. Specimens were homogenized for biochemical analysis; epididymal content of each rat was obtained immediately for semen analysis. Testes’ specimens were harvested, prepared and examined by light microscope examination. Results Induced hypothyroidism was noticed to cause histopathological, morphometric and biochemical changes in rat’s testes. LC protected the testicular specimens against such changes; it also improved the seminal quality and quantity as well as testicular structure and biochemistry. Conclusion Hypothyroidism could result in hazards to the structure of testis. Fortunately co-administration of LC might reduce such hazards.
In this paper, I try to focus on widely growing field of Management Science; and that, “Modeling of Management Issues “. Now days Business Simulation techniques are used to earn more profit from Business and this is only issues control future course of actions properly. By using models we can predict & control future course of action & situation. Modeling is not a new subject. It’s oldest technique, but widely used in Physical Sciences, like Chemistry, Physics, Electronics, Engineering field, But it’s again become vital after some time in Life Sciences, like Botany, Zoology, Bio-Chemistry, Bio-Tech and Medical field problem modeling and now in current world it’s also become very vital in Information Technology and Management subjects. Here one question is always arise, why such a modeling is needed, and where and when needed, and answer of this simple question is, considering some simple problems like ‘ to find out the width of a river (But your are not allowed to cross it), find out the temperature (but you are not allowed to use thermometer), means try to find out any Quantity or parameter/variable without existence or entity of that, and if virtual situation satisfied by using modeling technique, we implement that virtual model for actual situation. In last I want to conclude modeling is the heart of any branch of Education, weather its science, Arts, Commerce, Medical, Information Technology, Engineering or Management and in summaries form I want to say this paper is nothing but one of the theoretical model, which is for modeling of Management issues for perfect Business Simulation.
Environmental impact of anthropogenic activities from industrial sources, have become a threat to biodiversity. Water samples were collected from rivers around the flow station, and analysed from some physicochemical parameters and hydrocarbon contents. Result of the physicochemistry was reported for: pH (6.58± 0.04 - 6.76±0.01), conductivity (168.30±13.98 - 194.57±3.78 µS/cm), conductivity 8.29±0.04 - 10.66±0.02 NTU, salinity (0.07±0.00 - 0.09± 0.00 mg/l), and Total Solids (83.96±1.49 - 103.66±0.60mg/l). Other elemental analysis includes: sulphates (2.43±0.01 - 4.28 ±0.02 mg/l), nitrates (0.19±0.01 - 0.28±0.01 mg/l), carbonates (1.14±0.07 - 2.06±0.07 mg/l), calcium (8.45±0.10 - 11.70±0.25 mg/l), magnesium (1.14±0.07 - 2.56±0.03 mg/l), and sodium (4.37±0.15 - 5.62±0.03 mg/l). The values of THC and TPH were 0.92±0.08 - 1.51±0.03, and 0.37±0.13 - 0.76±0.07 mg/l respectively. Generally, the result indicated mild level of contamination in terms of Hydrocarbon contents. However, diagnostic data emerging for physicochemistry and some elemental property indicates the water is unfit for consumption. Notwithstanding, the order on contamination were reported as; downstream > midstream > upstream. Therefore this study concludes that there should be frequent monitoring of the recipient water bodies associated with the flow station in order to check anthropogenic activities, and conserve biodiversity.
Objectives: An association between the measles virus and Hodgkin lymphoma has been disclosed by our laboratory in Beer-Sheva, starting in 2003. We question the refutation of our study and the absence of interest among experts. Methodology: It was based on immunohistochemistry with commercial, as well as experimental anti-measles antibodies. It relied also on RT-PCR and in situ hybridization evidence of measles virus RNA. Key Results: At this stage (2004), the link between the virus and the lymphoma was essentially descriptive. The first and last response to our challenge appeared in 2007, in the form of doublet articles, in the same issue of a major cancer journal. The two European research groups responding, rejected categorically our findings by proposing different arguments. Major Conclusion: As reservations to these reactions became soon apparent, a series of papers from our laboratory were published. These articles concerned the evidence of a relationship between the measles virus and additional categories of cancers. Different malignancies in which this virus was not expressed at all, were also described. A further study suggested a mechanism by which the measles virus may activate lymphomagenesis in classic Hodgkin lymphoma. To our dismay, and in spite of repeated calls to verify the various results, no further response was obtained from international experts.
Background: Faculty of Medicine and Health sciences at University of Kassala, Sudan was established 1990. It adopts the traditional curricula, which implemented in preclinical (basic sciences) and clinical phases. This study was held to explore students' perception and attitudes towards the basic sciences. Methods: A descriptive cross-sectional study was conducted during April- August 2017 among 251 medical students. Self-administered questionnaire was used to collect data. It was collected and analyzed using SPSS 16.0. Results: A total of 251 of participants in different phases of education in faculty of medicine and health sciences were included in the study; preclinical 116 (46.2%), 113 clinical (45.0%), and 22 (8.8%) were in internship. 95 (37.8 %) were males and 156 (62.2%) were females. The study revealed that physiology was the most preferable subject. Students' satisfaction to syllabus for anatomy, physiology and biochemistry was 61.4%, 43%, and 28.7% respectively. However, 46.6% of students spent a long time to understand biochemistry and 33.1% considered it as overloaded syllabus. Participants showed poor ability to link between theoretical and practical work in case of biochemistry (26.7%), where as anatomy and physiology were represented by 76.9% and 42.2% respectively. Less than half of students were able to integrate the subjects of basic sciences and basic with clinical sciences. Conclusion: In this study, the students determined the difficulties of recalling of information, poor integration between basic and clinical sciences and even integration within the subject. Development of integrated curriculum is necessary to improve the quality of education.
Big data research has become popular and exciting studies in almost all scientific fields such as biology, chemistry, epidemiology, medicine and drug discovery. The various systems and platforms produce large amounts of data every day. It will be very helpful for the researchers and workers to deal with big data if the practical database and useful software are introduced in time. The Journal of Big Data Research (JBR) supplies an efficient and open access publishing platform for big data research. The first issue of JBR aims to foster the dissemination of high-quality big data studies in the biological, medical and chemical database as well as the new algorithm and software for big data processing. The database and computing framework are selected to introduce the development of big data in the biological, medicine and drug discovery. The mature and functional database can be serviced in big data research of scientific fields. It promotes the scientists to extract the useful and essential dataset from the massive data. The grid computing and cloud computing supplies a new paradigm that offers an effective framework of computing and services. The research papers are welcomed from the scopes of the practical database, new algorithm and software for big data studies. All these kinds of papers not only provide the effective application methods and platforms, but also give a good promising future for big data research.
Following ocular trauma and retinal detachment, gliotic changes in the retina may develop over the subsequent month, a process known as PVR (proliferative vitreoretinopathy). There have been no successful therapeutic interventions to inhibit PVR. The protein CTGF (Connective Tissue Growth Factor) has been associated with retinal PVR and other fibrotic diseases of the retina in clinical studies but the mechanistic link between different pathologies and retinal gliosis has not been determined. In addition, CTGF has been previously noted to be associated, in some cases, with YAP/TAZ (Yes-associated protein and Tafazzin protein complex), transcriptional regulatory proteins that change subcellular localization in response to mechanical cues, such as the stiffness of the underlying material. We have previously shown that the mRNA for CTGF is markedly (100-fold) upregulated in retinal Müller cells grown on soft substrates. In order to evaluate if the mechanism by which mechanotransduction modulating CTGF production in retinal Müller cells involves the YAP/TAZ complex, this study tests the influence of substrate stiffness on the time dependence of CTGF protein expression, as well as subcellular localization of YAP/TAZ using a conditionally-immortalized mouse retinal Müller cell line plated on laminin-coated, polyacrylamide substrates of varying elastic modulus. Changes were assayed using immunohistochemistry and ELISA (Enzyme-Linked ImmunoSorbent Assay). In retinal Müller cells, the relationship between elastic modulus and the pattern of CTGF protein expression was bimodal, with CTGF levels rising more rapidly for cells on hard substrates and more slowly for cells grown on soft substrates. In addition, nuclear localization of YAP/TAZ corresponded directly to the maximum CTGF expression.
Introduction Bovine papillomavirus (BPV) is the etiological agent of bovine papillomatosis, infectious and neoplastic disease, characterized by the presence of multiple papillomas that can regress spontaneously or to persist and progress to malignancies when in association with environmental cofactors. Although recognized that the BPV can induce DNA damages, the viral role following cancer initiation remains unresolved. Based on this, we stablished cell lines derived from cutaneous papilloma, fibropapilloma and esophageal carcinoma to study the BPV action on epithelial-mesenchymal transition (EMT). Our results showed strong evidences that the virus action can contribute to EMT and, therefore, metastasis. Aim In this study, we analyzed the expression levels of the EMT markers (cytokeratin 10, STAT3 Y705, Oct-3/4 and vimentin) in paraffin-embed samples, using the same tissues that originated the cell lines previous studied, aiming to validate the results observed using cell lines. Material and Methods Expression levels of these markers was analyzed by immunohistochemistry and the collagen composision by Picrosirius red staining. Results We verified an overexpression of these markers in fibroblastoid cells present into the epidermis and ketarinocyte-like cells into the dermis present in dermo-epidermal junction. These data reinforce our previous results using cell cultures, validating both systems (cell culture and paraffin-embed tissues) as useful models to study the natural history of BPV-infected lesions. Conclusion Altogether, the results from these systems indicate that the BPV promote the cancer progression and metastasis through the transdifferentiation of an epithelial to mesenchymal cells (EMT).
The mammary tumor is one of the most common cancer in female dogs and, at the present days, there is a big focus on the study of the relation between this kind of tumor in animals and the cells that stay around them, like the inflammatory cells. The objective of this study was to evaluate and show where the inflammatory cells stay in simple mammary carcinomas in female dogs by immunohistochemistry. Samples of simple mammary carcinomas (tumor group; n=26) and mammary gland samples without tumor (control group; n=18) were submitted to immunohistochemical analysis for the detection of T lymphocytes, macrophages, plasma cells and the MHC-II molecule. The mast cells were evaluated by the histochemical technique (toluidine blue). Lymphocytes, macrophages and mast cells were observed distributed in the tumor stroma. MHC-II was detected in tumor cells and in the inflammatory infiltrate. Plasma cells predominated in the peritumoral stroma. Macrophages differed significantly between the two groups and predominated in the tumor group. In the comparison between histological types of mammary carcinomas, mast cells differed significantly between solid tumors of the tubular / papillary types. The cytoplasmic immunodetection of MHC-II was suggested an inefficient antigen presentation. Some of the leukocytes present in the tumor infiltrate, appear to be exerting a pro-tumor effect and allowing the progression of tubular and papillary carcinomas. But in solid carcinomas (may be poorly immunogenic), as they had the lowest proportion of leukocytes present in the tumor site. More studies are necessary to confirm these results, such as the determination of the cytokine profile and the predominant leukocyte subpopulations in the tumor microenvironment.
Background: The diagnosis and treatment outcomes of Non- Hodgkin Lymphoma’s (NHL) in resource poor countries in the absence of routine molecular studies and immunohistochemistry is challenging. Methods: A retrospective review of case folders of NHL patients aged13 years and above. Information obtained from the case folders included age, sex, histological subtype, subtypes using the Working Formulation and WHO classifications. Treatment given and follow up information were also evaluated. Results: A total of 279 cases of NHL were identified within the study period. The mean age of the patients was 48.8 ± 17.0 years. The male to female ratio was approximately 1.5:1. The majority of cases seen (53%) were diffuse large B- cell lymphoma. Chronic lymphocytic leukaemia/ small lymphocytic lymphoma (22.2%) was the next most common subtype. Other sub types seen, in order of frequency, included diffuse mixed cell lymphoma (6.4%), gastric lymphomas (3.9%), mediastinal B- cell lymphoma (2.9%), Burkitt’s lymphoma (1.8%), splenic marginal zone B-cell lymphoma (1.1%), lymphoblastic lymphoma (1.1%), mucosa- associated lymphoid tissue (MALT) type B- cell lymphoma (0.7%) and follicular lymphoma (0.7%). Conclusion: This study provides an overview of the distribution of NHL subtypes and their outcomes in a resource constrained setting. Immunohistochemistry, cytogenetics and specific molecular studies which are important in characterization of NHLs, should be made affordable and accessible in low income countries.
Insulin receptor substrate (IRS) 1 and 2 are downstream signaling proteins that influence breast pathophysiology. IRS-1 promotes carcinoma cell proliferation; whereas IRS-2 regulates cell motility, invasion, and glycolysis. Our lab has shown that distinct cellular localization of IRS-2 also plays a role in carcinoma cell function. Oncotype DX (Genomic Health) (ODX) is a 21-gene expression profile used to classify carcinomas with low, intermediate, and high risk recurrence scores (RS). Our aim is to correlate expression and cellular localization of IRS proteins in breast carcinomas with their ODX RS. 97 breast carcinomas sent for ODX testing from 2006-2009 were collected and grouped according to their RS (low, intermediate or high). Immunohistochemistry for IRS-1/-2 was performed. Specific criteria were used to evaluate IRS staining patterns. Follow-up data, ranging from 3-6 years, was available. Statistical analysis was performed to correlate staining patterns of IRS-1/-2 with the three RS groups. IRS-1 staining, predominantly nuclear, did not significantly correlate with RS (P=.5645). IRS-2 expression patterns did show statistical significance amongst the three RS groups (P=.0371). Tumors with intermediate and low RS were more likely to exhibit punctate and diffuse cytoplasmic expression of IRS-2, and cell membrane expression was uncommon in this group. Expression and cellular localization of IRS proteins play an important role in breast cancer cell biology, and expression patterns for IRS-2 do demonstrate a significant correlation with ODX RS. Further studies are required to elucidate the significance of cellular localization of IRS-1/-2 proteins in breast carcinoma cells and their relationship to ODX scores.
The purpose of this study was to investigate the effect of cremophor RH-40 and polysorbate 80 with hydroxypropyl methylcellulose (HPMC) F4M on the development of formulations of intranasal erythropoietin with low sialic acid content (Neuro-EPO) as a neuroprotective agent. Parameters such as pH, osmolality, apparent viscosity, and protein concentration were controlled for minimizing the differences between formulations. All Neuro-EPO formulations showed similar behaviour in the physicochemistry quality control. However significant differences between formulations were observed in the permanent unilateral ischemia model. The formulations and the vehicles containing cremophor RH-40 showed higher neurotoxicity levels than those containing polysorbate 80 as a nonionic surfactant. Formulations containing HPMC F4M at 0.6% as a bioadhesive polymer showed higher levels of survival and better neurological status than those without the polymer. The formulations with polysorbate 80 and HPMC F4M showed a higher index of survival, smaller incidence of clinical signs of stroke, and similar behavior in the learning and the memory to the false injured animals used as control. These findings suggest that the intranasal pathway constitutes a safe and alternative route of access of the Neuro-EPO to the brain.
Background: Heart valves share developmental signaling pathways with cartilage and bone. While calcific aortic valve disease (CAVD) has been associated with valve calcification and stenosis, suggestive of osteogenesis, myxomatous mitral valve disease (MMVD) is characterized by net matrix degradation, exuberant deposition of proteoglycan, and valve regurgitation. Methods: We determined the presence of cartilage-abundant proteoglycan, aggrecan; cartilage-specific type II collagen; chondrogenic transcription factor, Sox9; and osteogenic transcription factor, Runx2 in human normal and myxomatous mitral valve leaflets by immunohistochemistry. Results and Conclusions: Myxomatous, but not normal, mitral valves demonstrated sharp focal areas that were abundant in aggrecan, type II collagen, and Sox9. These focal areas co-localized with areas of myxomatous pathologic change on Movat staining. Some cells in these areas had a round and hypertrophic morphology reminiscent of chondrocytes. Runx2 was only weakly present in normal and myxomatous mitral valves. These findings suggest a focal pathologic process in MMVD that mimics chondrogenesis.