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Molecular typing using repetitive sequenced-based PCR (rep-PCR) and hsp60 sequencing were applied to a collection of diverse Enterobacter cloacae complex isolates. To determine the most practical method for reference laboratories, we analyzed 71 E. cloacae complex isolates from sporadic and outbreak occurrences originating from 4 geographic areas. While rep-PCR was more discriminating, hsp60 sequencing provided a broader and a more objective geographical tracking method similar to multilocus sequence typing (MLST). In addition, we suggest that MLST may have higher discriminative power compared to hsp60 sequencing, although rep-PCR remains the most discriminative method for local outbreak investigations. In addition, rep-PCR can be an effective and inexpensive method for local outbreak investigation.

Background: Trigeminal neuralgia (TN) usually affects people over 50 years old. TN-related pains are short-lived, and the disease course is characterized by exacerbations and remissions. Sometimes chronic pain develops due to central sensitization. This is the first case report on the effectiveness of tapentadol in pain control in TN., Case Description: It is an instructive case history demonstrating the high effectiveness of tapentadol in a 55-year-old Caucasian male with severe [Visual Analogue Scale (VAS) 9/10] TN-related pain and a history of ineffective treatment with antiepileptic drugs. The neuralgia had occurred twice a year for the three preceding years, and typically the TN periods lasted 2-3 weeks with complete remissions between. Previously the patient had been treated with antiepileptic drugs (e.g., carbamazepine, phenytoin, clonazepam, gabapentin, and lamotrigine). However, he found all treatments to be ineffective and accompanied by unacceptable somnolence. Thus, a prolonged-release oral tapentadol was proposed at the beginning of the next relapse. After application of tapentadol, the patient reported a significant improvement. The severity of pain declined to VAS 6/10 (2nd day) and 4/10 (3rd day), and the attacks resolved entirely on the fourth day of treatment. He reported no side effects. The drug was discontinued after 14 days., Conclusions: Despite pain chronification, tapentadol was efficient and well tolerated in TN. Further research is needed to reveal tapentadol's efficacy in neuralgias.

Objective: This case report presents an uncommon case of hydrocolloid dressing efficacy in pain control in herpes zoster reactivation with vast epidermis damage., Methods: It is an instructive tale presenting the application of hydrocolloid dressing in a ripe old age woman with locally advanced breast cancer suffering from the fourth shingles reactivation., Results: The application of hydrocolloid dressing led to the rapid improvement of pain control (Visual Analogue Scale decreased from 9/10 to 4/10). It also improved the quality of life and promoted the rapid healing of damaged skin., Conclusion: In light of the described case, the application of hydrocolloid dressing could be considered in patients suffering from severe neuropathic pain in shingles, especially in severe cases. Further clinical studies are recommended., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: CXCL12/CXCR4 signaling is essential in cardiac development and repair, however, its contribution to aortic valve stenosis (AVS) remains unclear. In this study, we tested the role of endothelial CXCR4 on the development of AVS., Materials and Methods: We generated CXCR4 endothelial cell-specific knockout mice (EC CXCR4 KO) by crossing CXCR4 fl/fl mice with Tie2-Cre mice to study the role of endothelial cell CXCR4 in AVS. CXCR4 fl/fl mice were used as controls. Echocardiography was used to assess the aortic valve and cardiac function. Heart samples containing the aortic valve were stained using Alizarin Red for detection of calcification. Masson's trichrome staining was used for the detection of fibrosis. The apex of the heart samples was stained with wheat germ agglutinin (WGA) to visualize ventricular hypertrophy., Results: Compared with the control group, the deletion of CXCR4 in endothelial cells led to significantly increased aortic valve peak velocity and aortic valve peak pressure gradient, with decreased aortic valve area and ejection fraction. EC CXCR4 KO mice also developed cardiac hypertrophy as evidenced by increased diastolic and systolic left ventricle posterior wall thickness (LVPW), cardiac myocyte size, and heart weight (HW) to body weight (BW) ratio. Our data also confirmed increased microcalcifications, interstitial fibrosis, and thickened valvular leaflets of the EC CXCR4 KO mice., Conclusion: The data collected throughout this study suggest the deletion of CXCR4 in endothelial cells is linked to the development of aortic valve stenosis and left ventricular hypertrophy. The statistically significant parameters measured indicate that endothelial cell CXCR4 plays an important role in aortic valve development and function. We have compiled compelling evidence that EC CXCR4 KO mice can be used as a novel model for AVS., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Winnicki, Gadd, Ohanyan, Hernandez, Wang, Enrick, McKillen, Kiedrowski, Kundu, Kegecik, Penn, Chilian, Yin and Dong.)

Objective: We describe a case of persisting readings from a fingertip pulse oximeter (FPO) in an elderly cachectic woman with pancreatic cancer, who fulfilled all classical criteria of death., Methods: It is an instructive example of a home hospice patient who died during the physician's intervention. Although all classical signs of death had been confirmed several times, a portable FPO continued to indicate satisfactory saturation and pulse readings for the following 30 min., Results: Our case report confirms that the classical criteria of death might sometimes be faulty. The application of a portable FPO prevented a premature declaration of death., Conclusion: In exceptional cases, even the most careful physical examination may erroneously indicate that a person is dead. A residual cardiac output and gas exchange may be preserved and revealed by FPO readings. In doubtful situations, FPO can provide additional information and prevent a premature declaration of death., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Colorectal cancer has a devastating effect on the quality of life, and the treatment of active intestinal bleeding in colorectal cancer is a real challenge at the end of life. This case report presents a spectacular effect of an unusual palliative treatment strategy in a middle-aged home hospice patient with severe pain and persistent duodenal bleeding secondary to its neoplastic infiltration. Palliative radiotherapy (RT) significantly improved pain control, terminated the duodenal bleeding, and allowed successful treatment of deep vein thrombosis, previously impossible because of the bleeding. It also made the patient independent of otherwise unavoidable transfusions, thus improving his quality of life. In our patient, RT played a leading role in restoring general fitness and, accordingly, mental state improvement. Our case demonstrates that palliative RT may be a valuable treatment option in cases similar to ours. Still, careful assessment of risks and benefits is always mandatory., (Copyright © 2020 American Academy of Hospice and Palliative Medicine. Published by Elsevier Inc. All rights reserved.)

Cancer cachexia (CC) is a progressive loss of muscle mass (with or without a decrease of adipose tissue). Gradual deterioration of the patient's fitness is resistant to nutritional intervention. The biochemical foundation of observed catabolism, detrimental protein, and energy balance is complex. However, the generalized inflammatory response plays a vital role. It is a kind of cytokine storm, which involves increased activity of TNF-α, IL-1, IL-6, and INF-γ. Pharmacological treatment of cachexia consists mainly of progestagens and glucocorticosteroids. Still, the assessment of new options limiting the harmful impact of cachexia could be beneficial. Chloroquine (CQ) and hydroxychloroquine (HCQ) are old antimalarial agents endowed with immunomodulatory properties. Being potent autophagy inhibitors, they could lead to a form of intracellular starvation in both cytokine-releasing cells and cancer cells, thus limiting the harmful impact of CC. CQ and HCQ are also efficient in particular connective tissue disorders. They have gained special attention since the World Health Organization announced the coronavirus disease 2019 (COVID-19) pandemic. According to initial reports, people with a severe inflammatory reaction showed significant benefits. Possibly they could not be attributed to the antiviral activity alone. It is worth noting that the cytokine storm in COVID-19, connective tissue disorders, and cancer cachexia share some similarities. Therefore, we hypothesize that low doses of CQ/HCQ may prove efficient in cancer cachexia., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Oxidative stress (OS) is recognized as disturbance of cellular equilibrium between reactive oxygen species (ROS) formation and their elimination by antioxidant defense systems. One example of ROS-mediated damage is generation of potentially mutagenic DNA precursor, 8-oxodGTP. In human cells genomic 8-oxodGTP incorporation is prevented by the MutT homologue 1 (MTH1 or hMTH1 for human MTH1) protein. It is well established that malignant cells, including thyroid cancer cells, require hMTH1 for maintaining proliferation and cancerous transformation phenotype. Above observations led to the development of hMTH1 inhibitors as novel anticancer therapeutics. In the current study we present extensive analysis of oxidative stress responses determining sensitivity to hMTH1 deficiency in cultured thyroid cells. We observe here that hMTH1 depletion results in downregulation of several glutathione-dependent OS defense system factors, including GPX1 and GCLM, making some of the tested thyroid cell lines highly dependent on glutathione levels. This is evidenced by the increased ROS burden and enhanced proliferation defect after combination of hMTH1 siRNA and glutathione synthesis inhibition. Moreover, due to the lack of data on hMTH1 expression in human thyroid tumor specimens we decided to perform detailed analysis of hMTH1 expression in thyroid tumor and peri-tumoral tissues from human patients. Our results allow us to propose here that anticancer activity of hMTH1 suppression may be boosted by combination with agents modulating glutathione pool, but further studies are necessary to precisely identify backgrounds susceptible to such combination treatment., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Introduction: Thyroid iodide transporters, Na + /I - symporter (NIS) and pendrin (PDS), are responsible for supplying this vital micronutrient for thyroid hormone synthesis by thyroid peroxidase (TPO). Both proteins were shown to be expressed, apart from the thyroid, also in other human tissues, including lactating mammary gland. NIS expression in human breast cancers has been widely studied. On the other hand, until now PDS mRNA levels in breast tumor tissue have been estimated only in high throughput analyses. Previously, we have observed that TPO is expressed in normal and cancerous human breast tissues and shows enzymatic activity. However, biochemical activity of TPO in human breast cancer cells requires iodide transport by NIS and PDS. Therefore, to extend our previous study on TPO expression and function in human breast tumors we performed analysis of NIS and PDS levels in the same group of patients., Material and Methods: The study involved detection of NIS and PDS protein levels by immunohistochemistry and Western blotting, as well as mRNA levels by real-time quantitative polymerase chain reaction., Results: Here we provide direct evidence that NIS and PDS are expressed in human breast cancer tissue, with NIS levels being increased and PDS levels decreased in tumor tissue. Interestingly, PDS mRNA levels in breast cancer tissue seem to be influenced by the estrogen receptor status and age of the patients, while NIS mRNA levels were dependent on histological type of the tumor., Conclusions: This study provides valuable information important for consideration in diagnostic or therapeutic application of radioiodine in breast cancer management., Competing Interests: The authors declare no conflict of interest., (Copyright: © 2019 Termedia & Banach.)

Diabetes is a risk factor for worse outcomes following acute myocardial infarction (AMI). In this study, we tested the hypothesis that SDF-1:CXCR4 expression is compromised in post-AMI in diabetes, and that reversal of this defect can reverse the adverse effects of diabetes. Mesenchymal stem cells (MSC) isolated from green fluorescent protein (GFP) transgenic mice (control MSC) were induced to overexpress stromal cell-derived factor-1 (SDF-1). SDF-1 expression in control MSC and SDF-1-overexpressing MSC (SDF-1:MSC) were quantified using enzyme-linked immunosorbent assay (ELISA). AMI was induced on db/db and control mice. Mice were randomly selected to receive infusion of control MSC, SDF-1:MSC, or saline into the border zone after AMI. Serial echocardiography was used to assess cardiac function. SDF-1 and CXCR4 mRNA expression in the infarct zone of db/db mice and control mice were quantified. Compared to control mice, SDF-1 levels were decreased 82%, 91%, and 45% at baseline, 1 day and 3 days post-AMI in db/db mice, respectively. CXCR4 levels are increased 233% at baseline and 54% 5 days post-AMI in db/db mice. Administration of control MSC led to a significant improvement in ejection fraction (EF) in control mice but not in db/db mice 21 days after AMI. In contrast, administration of SDF-1:MSC produced a significant improvement in EF in both control mice and db/db mice 21 days after AMI. The SDF-1:CXCR4 axis is compromised in diabetes, which appears to augment the deleterious consequences of AMI. Over-express of SDF-1 expression in diabetes rescues cardiac function post AMI. Our results suggest that modulation of SDF-1 may improve post-AMI cardiac repair in diabetes. Stem Cells Translational Medicine 2018;7:115-124., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background and Aim: The aim of the study was to assess the impact of individualised nutritional intervention based on the DASH diet (Dietary Approaches to Stop Hypertension) on the nutritional status, blood pressure, and selected biochemical parameters of obese/overweight patients with primary arterial hypertension., Methods: A total of 131 participants were randomised to the DASH intervention group (DIG; n = 69, 33 males) or the control group (CG; n = 62, 32 males). A three-month nutritional intervention was carried out in the DIG group, while the control group received only standard recommendations. Body weight, height, waist and hip circumference, body composition, blood pressure, serum glucose, and insulin and leptin concentrations were measured at the baseline and after the intervention., Results: Sixty-four (92.8%) participants in the intervention and 62 (100%) in the control group completed the study. In the DIG group a significant decrease in body mass, systolic and diastolic blood pressure, body fat content, fasting glucose, insulin, and leptin concentrations were observed in comparison to the control group (p < 0.05)., Conclusions: The DASH dietary intervention provides significant benefits to overweight/obese patients with primary hypertension.

Celiac disease affects about 1% of the population. Since most Polish households have a broadband Internet connection, a lot of people use web resources to learn about health and disease. YouTube service (www.youtube.com) offers a lot of videos concerning celiac disease. However, the credibility of the Polish videos available on YouTube and concerning celiac disease has never been analyzed., Aim: The aim of the study was to determine whether the YouTube service offers valuable content for Polish people affected by celiac disease., Materials and Methods: One hundred and fifty-four unique videos devoted to celiac disease and available in the Polish language were identified and critically assessed. Each video was categorized due to its topic(s), and evaluated for its credibility by two independent researchers., Results: In general, 127 (82.5%) videos were found to be credible. The most credible categories of content presented organizations and events related to celiac disease/celiac society, followed by culinary recipes (100.0, 100.0, and 95.6% of credible videos, respectively). The least trustworthy categories were devoted to pathobiology and advertisements (55.6 and 54.3% of credible videos, respectively)., Conclusions: YouTube service can serve as a supplementary source of knowledge for people affected by celiac disease, after careful selection of trustworthy content.

Transplantation of adult stem cells into myocardial tissue after acute myocardial infarction (AMI), has been shown to improve tissue recovery and prevent progression to ischemic cardiomyopathy. Studies suggest that the effects of mesenchymal stem cells (MSC) are due to paracrine factors released by MSC, as the benefits of MSC can be achieved through delivery of conditioned media (CM) alone. We previously demonstrated that downregulation of Dab2 enhances MSC cardiac protein expression and improves cardiac function after AMI following MSC engraftment. In order to define the molecular mechanisms that regulate MSC secretome, we analyzed gene arrays in MSC following downregulation of Dab2 via TGFβ1 pretreatment or transfection with Dab2:siRNA or miR-145. We identified 23 genes whose expressions were significantly changed in all three conditions. Among these genes, we have initially focused our validation and functional work on calcium/calmodulin-dependent protein kinase kinase-1 (CAMKK1). We quantified the effects of CAMKK1 overexpression in MSC following injection of CM after AMI. Injections of CM from MSC with CAMKK1 over-expression correlated with an increase in vascular density (CAMKK1 CM: 2,794.95 ± 44.2 versus Control: 1,290.69 ± 2.8 vessels/mm 2 ) and decreased scar formation (CAMKK1 CM 50% ± 3.2% versus Control: 28% ± 1.4%), as well as improved cardiac function. Direct overexpression of CAMKK1 in infarcted tissue using a CAMKK1-encoding plasmid significantly improved ejection fraction (CAMKK1: 83.2% ± 5.4% versus saline: 51.7% ± 5.8%. Baseline: 91.3% ± 4.3%) and decreased infarct size after AMI. Our data identify a novel role for CAMKK1 as regulator of the MSC secretome and demonstrate that direct overexpression of CAMKK1 in infarcted cardiac tissue, results in therapeutic beneficial effects. Stem Cells Translational Medicine 2017;6:1759-1766., (© 2017 The Authors Stem Cells Translational Medicine published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.)

Background: Thyroid peroxidase (TPO) is essential for physiological function of the thyroid gland. The high prevalence of thyroid peroxidase antibodies (TPOAbs) in patients with breast cancer and their protective role had previously been demonstrated, indicating a link between breast cancer and thyroid autoimmunity. Recently, TPO was shown to be present in breast cancer tissue samples but its antigenicity has not been analyzed., Methods: In this study, we investigated TPO expression levels in a series of fifty-six breast cancer samples paired with normal (peri-tumoral) tissue and its antigenic activity using a panel of well-characterized murine anti-human TPOAbs., Results: We have shown that TPO transcripts were present in both normal and cancer tissue samples, although the amounts in the latter were reduced. Additionally, we observed that TPO levels are lower in more advanced cancers. TPO protein expression was confirmed in all tissue samples, both normal and cancerous. We also found that the antigenicity of the immunodominant regions (IDRs) in breast TPO resembles that of thyroid TPO, which is crucial for effective interactions with human TPOAbs., Conclusions: Expression of TPO in breast cancer together with its antigenic activity may have beneficial effects in TPOAb-positive breast cancer patients. However, further studies are needed to confirm the beneficial role of TPOAbs and to better understand the underlying mechanism.

Colorectal carcinoma (CRC) is a diet-related disease. The high incidence of CRC is related to the excessive consumption of certain foods and a westernized lifestyle of contemporary societies. Obesity and low physical activity remain significant risk factors for CRC development. Molecular pathogenesis of CRC is fairly well recognized, which contributes to the formulation of hypotheses and conducting research on the participation of nutritional factors in the CRC development. This contribution remains diverse and for many food components a protective effect on colorectal carcinogenesis has been demonstrated. The aim of this review is to present a relationship between consumption of two selected components of the diet - fiber and milk - and the development of colorectal carcinoma, based on the review of literature., (© 2016 MEDPRESS.)

The development of colorectal carcinoma is a multistep process of accumulation of mutations and epigenetic changes associated with DNA repair, proliferation, apoptosis, intra- and extracellular signaling, adhesion and other physiological functions of cells and tissues. A long period of development, high colorectal carcinoma-related mortality as well as significant social and economic costs due to this condition are prerequisites for seeking efficient methods of cancer prevention, including nutritional approach. A number of bioactive components of food is extensively tested for antitumor activity, however limited number of reliable studies on humans impedes the formulation of unequivocal nutritional recommendations. Plant products represent a rich source of numerous phytochemicals endowed with anticancer potential due to, first of all, their free radical scavenger activity. The purpose of this paper was to present the relationship between consumption of selected foods reach in numerous bioactive compounds with proven or putative anticancer activity - vegetables, fruits, coffee and tea - and the development of colorectal carcinoma, based on selected studies. A number of controversies related to the anti-tumor potential of the above ingredients was also discussed.

The stromal cell-derived factor-1 (SDF-1):CXCR4 is important in myocardial repair. In this study we tested the hypothesis that early upregulation of cardiomyocyte CXCR4 (CM-CXCR4) at a time of high myocardial SDF-1 expression could be a strategy to engage the SDF-1:CXCR4 axis and improve cardiac repair. The effects of the hypoxia inducible factor (HIF) hydroxylase inhibitor dimethyloxalylglycine (DMOG) on CXCR4 expression was tested on H9c2 cells. In mice a myocardial infarction (MI) was produced in CM-CXCR4 null and wild-type controls. Mice were randomized to receive injection of DMOG (DMOG group) or saline (Saline group) into the border zone after MI. Protein and mRNA expression of CM-CXCR4 were quantified. Echocardiography was used to assess cardiac function. During hypoxia, DMOG treatment increased CXCR4 expression of H9c2 cells by 29 and 42% at 15 and 24 h, respectively. In vivo DMOG treatment increased CM-CXCR4 expression at 15 h post-MI in control mice but not in CM-CXCR4 null mice. DMOG resulted in increased ejection fraction in control mice but not in CM-CXCR4 null mice 21 days after MI. Consistent with greater cardiomyocyte survival with DMOG treatment, we observed a significant increase in cardiac myosin-positive area within the infarct zone after DMOG treatment in control mice, but no increase in CM-CXCR4 null mice. Inhibition of cardiomyocyte death in MI through the stabilization of HIF-1α requires downstream CM-CXCR4 expression. These data suggest that engagement of the SDF-1:CXCR4 axis through the early upregulation of CM-CXCR4 is a strategy for improving cardiac repair after MI., (Copyright © 2016 the American Physiological Society.)

Exposure to hand-transmitted vibration in the work-place can result in the loss of sensation and pain in workers. These effects may be exacerbated by pre-existing conditions such as diabetes or the presence of primary Raynaud's phenomena. The goal of these studies was to use an established model of vibration-induced injury in Zucker rats. Lean Zucker rats have a normal metabolic profile, while obese Zucker rats display symptoms of metabolic disorder or Type II diabetes. This study examined the effects of vibration in obese and lean rats. Zucker rats were exposed to 4h of vibration for 10 consecutive days at a frequency of 125 Hz and acceleration of 49 m/s(2) for 10 consecutive days. Sensory function was checked using transcutaneous electrical stimulation on days 1, 5 and 9 of the exposure. Once the study was complete the ventral tail nerves, dorsal root ganglia and spinal cord were dissected, and levels of various transcripts involved in sensorineural dysfunction were measured. Sensorineural dysfunction was assessed using transcutaneous electrical stimulation. Obese Zucker rats displayed very few changes in sensorineural function. However they did display significant changes in transcript levels for factors involved in synapse formation, peripheral nerve remodeling, and inflammation. The changes in transcript levels suggested that obese Zucker rats had some level of sensory nerve injury prior to exposure, and that exposure to vibration activated pathways involved in injury and re-innervation., (Published by Elsevier B.V.)

We present an unusual case of colon cancer development in bowel segment involved with lobular breast carcinoma infiltration. 80 year old Caucasian woman was diagnosed with right colon carcinoma due to rectal bleeding and obstructive symptoms. She had nine years clinical history of lobular, well differentiated breast cancer with five years of postoperative tamoxifen therapy, disseminating to bones and pleural cavities two years prior to hemicolectomy. On microscopic examination under the colonic adenocarcinoma and in the whole length of the resected bowel segment, massive infiltration of lobular carcinoma was discovered. She remains alive under the palliative hormone and chemotherapy. In our paper we discuss clinical and pathological issues concerning metastases of breast cancer into the gastrointestinal tract as well as rare colocalization of colonic and breast cancers within the same intestinal segment. Review of the literature is also presented accordingly.

Mercury is a silvery-white chemically active transition metal without known physiological role. It is also a toxin accumulated in living organisms--especially in the aquatic creatures (fish and shellfish). Mercury compounds are involved in biogeochemical cycles (especially atmospheric and hydrobiologic), and thus they become contaminants of food. Such process is facilitated by the increasing environmental chemization. Toxic effects of mercury compounds result from their high affinity to sulfur (sulfhydryl groups of amino acids), accumulation in parenchymal organs, metallic mercury lipophilicity as well as long biological half-life period. In Poland the major sources of mercury exposure in diet are fish products and mushrooms. The role of mercury in human toxicology was presented in the work, along with a review of the literature concerning mercury content in selected food products in Poland. In general, most of foods do not pose a threat to consumers' health. Some restrictions in the amount of predatory fish and mushrooms consumed by pregnant and breastfeeding women as well as small children should be however recommended.

In 2012 the updated guidelines for the treatment of gout were published by the American College of Rheumatology (ACR), which underline the necessity of comprehensive treatment in this condition. According to the European League Against Rheumatism (EULAR), treatment of comorbidities, lifestyle modifications and proper diet may be of significant importance. In the primary care settings in Poland there is virtually no access to qualified dieticians. The nutritional counseling is sometimes implemented--usually to a very limited extent--by primary care physicians. It is believed that proper diet may improve the prognosis and quality of life in patients with gout. The aim of the work is to present the principles of nutrition therapy in gout and hyperuricemia, in the context of their pathogenesis. The key principles of nutrition therapy in the above mentioned conditions include a restriction of purine amount in the diet and reaching the proper body weight. Optimal hydration and alcohol elimination are also beneficial. Furthermore, some food ingredients can affect the plasma level of uric acid in the mechanisms irrelevant of their purine load.

Introduction: The aim of the study was to evaluate the impact of sex, age, family history and distal findings on the risk of proximal advanced neoplasia (cancer or advanced adenoma) in the large bowel., Material and Methods: Records for 10 111 asymptomatic participants of the Colonoscopy Screening Program (CSP), recruited from the Warsaw region between 2000 and 2004, were analyzed. A multivariate logistic regression model was used to estimate the impact of sex, age, family history and most advanced distal lesions on the occurrence of proximal advanced neoplasia. To enhance comparability of the study two definitions of the proximal colon were applied - either the splenic flexure (1(st)) or the bend between the descending and sigmoid colon (2(nd) definition) represented the boundary., Results: One hundred and thirty-three (1(st)) and 167 patients (2(nd) definition) were found to have at least one advanced neoplastic lesion in the proximal part, respectively. Eleven and 14 patients were found to have carcinoma, while in 130 and 163 patients at least one proximal advanced adenoma appeared. Men were at twice as high risk of having advanced neoplasia in the proximal colon than women (OR = 1.94, 95% CI: 1.31-2.87, p = 0.001 or OR = 1.69, 95% CI: 1.20-2.40, p = 0.003, respectively). The presence of distal advanced neoplastic lesions was associated with 3.5 times higher risk of proximal advanced neoplasia (OR = 3.58, 95% CI: 2.00-6.43, p < 0.0001 or OR = 3.41, 95% CI: 1.95-5.96, p < 0.0001), respectively., Conclusions: The results may confirm some limitation of flexible sigmoidoscopy in the screening settings in comparison with colonoscopy, at least in men and people with distal advanced neoplasia.

Podoplanin (PDPN), a mucin-type transmembrane glycoprotein specific to the lymphatic system is expressed in a variety of human cancers, and is regarded as a factor promoting tumor progression. The purpose of this study was to elucidate the molecular role of PDPN in the biology of thyroid cancer cells. PDPN expression was evaluated in primary thyroid carcinomas and thyroid carcinoma cell lines by RT-qPCR, Western blotting, IF and IHC. To examine the role of podoplanin in determining a cell's malignant potential (cellular migration, invasion, proliferation, adhesion, motility, apoptosis), a thyroid cancer cell line with silenced PDPN expression was used. We observed that PDPN was solely expressed in the cancer cells of 40% of papillary thyroid carcinoma (PTC) tissues. Moreover, PDPN mRNA and protein were highly expressed in PTC-derived TPC1 and BcPAP cell lines but were not detected in follicular thyroid cancer derived cell lines. PDPN knock-down significantly decreased cellular invasion, and modestly reduced cell migration, while proliferation and adhesion were not affected. Our results demonstrate that PDPN mediates the invasive properties of cells derived from papillary thyroid carcinomas, suggesting that podoplanin might promote PTC progression.

Aim of the Study: Cyclooxygenase-2 (COX-2) expression has been observed in a substantial percentage of classical adenomas of the large bowel. The aim of the study was to assess and compare the expression of COX-2 in serrated polyps of the colon., Material and Methods: One hundred and nineteen serrated polyps were analyzed. There were 83 hyperplastic polyps (HP), 19 sessile serrated polyps (SSP) and 17 traditional serrated adenomas (TSA). COX-2 expression was assessed semi-quantitatively (0-2) and each lesion was fully characterized in terms of anatomical location, size, histology, age and sex of the patient. The general estimating equation (GEE) model with logit link was used in the statistical analysis., Results: Epithelial expression of COX-2 was found in 85/119 serrated polyps (71.43%): 57/83 (68.67%) HP, 16/19 (84.21%) SSP, and 12/17 (70.59%) TSA. In HP and SSP it was predominantly of weak (49/83 HP, 12/19 SSP), whereas in TSA it was mainly of medium/strong intensity (8/17). The TSA category was associated with more frequent COX-2 expression (OR = 7.00, 95% CI: 1.49-32.88, p = 0.014) than HP, but such relation was not found for SSP vs. HP (p > 0.1). No associations between COX-2 expression and clinical parameters were found., Conclusions: Immunohistochemical COX-2 expression cannot serve as a diagnostic adjunct to differentiate HP and SSP.

Like many malignancies, the development of colorectal carcinoma (CRC) can be considered as an imbalance between the compromised process of programmed cell death (apoptosis) and excessive, uncontrolled proliferation. Several mutations and epigenetic alterations are acquired during colorectal carcinogenesis. These are responsible for the cell cycle regulation, cellular sensitivity to pro- and antiapoptotic factors, cell proliferation, angiogenesis, invasiveness, as well as metastatic potential. The molecular alterations, along with their morphological expressions, have been recognised in detail, and most of the CRC cases can be attributed to either adenoma-carcinoma or serrated neoplasia pathways: in the first, the antiapoptotic features prevail; while in the second, the proliferative activity is of the utmost importance. The aim of the work is to discuss the influence of selected drugs and dietary compounds on the proliferation and apoptosis in CRC.

Rationale: Stage specific embryonic antigen 1+ (SSEA1+) cells have been described as the most primitive mesenchymal progenitor cell in the bone marrow. Cardiac injury mobilizes SSEA1+ cells into the peripheral blood but their in vivo function has not been characterized., Objective: We generated animals with chimeric bone marrow to determine the fate and function of bone marrow SSEA1+ cells in response to acute cardiac pressure overload., Methods and Results: Lethally irradiated mice were transplanted with normal bone marrow where the wild-type SSEA1+ cells were replaced with green fluorescent protein (GFP) SSEA1+ cells. Cardiac injury was induced by trans-aortic constriction (TAC). We identified significant GFP+ cell engraftment into the myocardium after TAC. Bone marrow GFP+ SSEA1 derived cells acquired markers of endothelial lineage, but did not express markers of c-kit+ cardiac progenitor cells. The function of bone marrow SSEA1+ cells after TAC was determined by transplanting lethally irradiated mice with bone marrow depleted of SSEA1+ cells (SSEA1-BM). The cardiac function of SSEA1-BM mice declined at a greater rate after TAC compared to their complete bone marrow transplant counterparts and was associated with decreased bone marrow cell engraftment and greater vessel rarefication in the myocardium., Conclusions: These results provide evidence for the recruitment of endogenous bone marrow SSEA1+ cells to the myocardium after TAC. We demonstrate that, in vivo, bone marrow SSEA1+ cells have the differentiation potential to acquire endothelial lineage markers. We also show that bone marrow SSEA1+ deficiency is associated with a reduced compensatory capacity to cardiac pressure overload, suggesting their importance in cardiac homeostasis. These data demonstrate that bone marrow SSEA1+ cells are critical for sustaining vascular density and cardiac repair to pressure overload.

Diagnostic and prognostic significance of α-methylacyl-CoA racemase (AMACR) has been established in many human cancers. Its correlation with clinical and pathologic data in gastric cancer has not been fully elucidated and its impact on surveillance has not been studied thus far. We analyzed consecutive gastric cancer cases in terms of AMACR expression and clinical/pathologic characteristics and followed patients' postoperative history. AMACR was expressed in 94/164 gastric cancers (57.3%). We did not find correlation between AMACR expression and sex, age, location, histologic type, pTN staging, vascular and nerve sheaths invasion. Overall disease-free survival tended to be worse in AMACR-positive patients (P=0.062), and in adenocarcinoma subgroup, it was significantly shorter (P=0.021). AMACR expression might represent promising adverse prognostic factor in gastric cancer, particularly in adenocarcinoma histologic type.

Background Aims: Acute cardiac injury results in the activation and recruitment of resident and non-cardiac stem cells. In this study we sought to define the pattern of peripheral stem cells and resident cardiac stem cell (CSC) activation induced acutely by cardiac pressure overload (PO)., Methods: PO was induced in mice by transaortic constriction (TAC). CSC, endothelial progenitor cells (EPC), hematopoietic stem cells (HSC) and stage-specific embryonic antigen (SSEA)-1(+) cells were profiled in the heart, spleen and bone marrow after TAC by flow cytometry., Results: The combination of a systemic and local stem cell response resulted in increases in SSEA-1 (+) cells and EPC in the heart 7 and 14 days post-TAC, respectively. Locally, modest SSEA-1(+) proliferation at 4 days preceded the elevated myocardial stem cell number. We observed no significant proliferation of EPC and CSC in the heart. The systemic stem cell response was characterized by a biphasic loss of splenic SSEA-1(+) cells at 2 and 7 days post-TAC and loss of bone marrow and spleen EPC at 4 and 7 days, respectively. Spleen size changed dynamically after TAC. A negligible response of HSC to TAC was observed. Significant EPC and SSEA-1(+) proliferation in the bone marrow and spleen occurred only after their local levels were decreased., Conclusions: Our results demonstrate that an orchestrated systemic stem cell response (EPC and SSEA-1 (+) ) takes place in response to TAC. The increase of SSEA-1(+) cells and EPC in the heart in response to pressure is likely to be because of a combination of local proliferation and stem cell recruitment.

Introduction: During the last decades, the proximal shift in the distribution of colorectal carcinomas (CRCs) has been described. It is uncertain whether the shift is the result of actual changes in CRC incidence or reflects population aging. Most CRCs develop as a result of malignant progression of benign epithelial neoplasms--advanced adenomas (AA)., Objectives: The aim of the study was to investigate whether the proximal shift of AA occurs over time., Patients and Methods: Two databases were used. The first one (RETRO) included consecutive patients of the Department of Gastroenterology treated between the years 1981 and 1994. The secondone (Colonoscopy Screening Program--CSP) included asymptomatic participants of the colonoscopy screening program recruited between 2000 and 2004 from the Warsaw region. Only patients with AA who underwent total colonoscopy were included in the analysis. AA was defined as adenoma of 10 mm or more in diameter, with high-grade neoplasia, and villous or tubulovillous morphology, or any combination of the above features. The analysis was conducted using 2 different definitions of the proximal segment in the large intestine--either splenic flexure or the bend between the descending and sigmoid colon. To compare the distribution of AA, a multiple logistic regression model was used., Results: 41 of 200 patients (20.5%) in RETRO and 122 of 430 patients (28.4%) in CSP group, respectively, were found to have AA located proximally to the splenic flexure. No proximal shift of AA was found after age and sex adjustment (P>0.1)., Conclusions: The risk of having proximal AA was similar in both groups. The results suggest the lack of proximal shift in the distribution of advanced colorectal adenomas.

The local route of stem cell administration utilized presently in clinical trials for stress incontinence may not take full advantage of the capabilities of these cells. The goal of this study was to evaluate if intravenously injected mesenchymal stem cells (MSCs) home to pelvic organs after simulated childbirth injury in a rat model. Female rats underwent either vaginal distension (VD) or sham VD. All rats received 2 million GFP-labeled MSCs intravenously 1 hour after injury. Four or 10 days later pelvic organs and muscles were imaged for visualization of GFP-positive cells. Significantly more MSCs home to the urethra, vagina, rectum, and levator ani muscle 4 days after VD than after sham VD. MSCs were present 10 days after injection but GFP intensity had decreased. This study provides basic science evidence that intravenous administration of MSCs could provide an effective route for cell-based therapy to facilitate repair after injury and treat stress incontinence.

We previously demonstrated that transient stromal cell-derived factor-1 alpha (SDF-1) improved cardiac function when delivered via cell therapy in ischemic cardiomyopathy at a time remote from acute myocardial infarction (MI) rats. We hypothesized that non-viral gene transfer of naked plasmid DNA-expressing hSDF-1 could similarly improve cardiac function. To optimize plasmid delivery, we tested SDF-1 and luciferase plasmids driven by the cytomegalovirus (CMV) promoter with (pCMVe) or without (pCMV) translational enhancers or α myosin heavy chain (pMHC) promoter in a rodent model of heart failure. In vivo expression of pCMVe was 10-fold greater than pCMV and pMHC expression and continued over 30 days. We directly injected rat hearts with SDF-1 plasmid 1 month after MI and assessed heart function. At 4 weeks after plasmid injection, we observed a 35.97 and 32.65% decline in fractional shortening (FS) in control (saline) animals and pMHC-hSDF1 animals, respectively, which was sustained to 8 weeks. In contrast, we observed a significant 24.97% increase in animals injected with the pCMVe-hSDF1 vector. Immunohistochemistry of cardiac tissue revealed a significant increase in vessel density in the hSDF-1-treated animals compared with control animals. Increasing SDF-1 expression promoted angiogenesis and improved cardiac function in rats with ischemic heart failure along with evidence of scar remodeling with a trend toward decreased myocardial fibrosis. These data demonstrate that stand-alone non-viral hSDF-1 gene transfer is a strategy for improving cardiac function in ischemic cardiomyopathy.

Homing of osteogenic cells through the systemic circulation represents an alternative to traditional orthopedic tissue engineering approaches that focus on local cell populations. We hypothesize that expression of the chemokine, stromal cell-derived factor-1 (SDF-1) or monocyte chemotactic protein-3 (MCP-3) may enhance homing of osteogenic cells into sites of fracture repair, as both have demonstrated promise in recruitment of marrow stromal cells (MSCs). This hypothesis was tested by transplantation of culture expanded MSCs expressing these factors adjacent to a fracture site on a collagen scaffold. One green fluorescent protein positive (GFP+) and one wild-type mouse were surgically conjoined as parabiots at 7-8 weeks of age. Fibular osteotomy was performed 4 weeks after parabiosis on the hind limb of the wild-type mouse. Mice were randomly allocated to receive one of the following five treatments: control (no scaffold), empty scaffold (no cells), or scaffold containing MSCs, scaffold containing MSCs expressing SDF-1, or scaffold containing MSCs expressing MCP-3. Fracture callus was harvested 2 weeks after injury, and analyzed with confocal microscopy and cell-counting software. When compared to fracture callus treated with nontransfected MSCs, the fracture callus of mice treated with both SDF-1 and MCP-3 secreting MSCs demonstrated a significant increase in the number of both GFP+ cells (p = 0.0003, p = 0.02) and GFP+ /AP+ cells (p = 0.0005, p = 0.01). These data suggest that homing of osteogenic cells from systemic circulation participate in fracture repair and that homing pathways might be modulated to enhance the contribution of circulating progenitors at the site of skeletal injury., (Copyright © 2011 Orthopaedic Research Society.)

Rationale: Hypoxia inducible factor (HIF)-1alpha is a transcription factor stabilized by hypoxia. It regulates cytokines involved in the inflammatory response after ischemia and affects white blood cell (WBCs) function. The effect of HIF-1alpha on WBC function and inflammation following myocardial infarction (MI) is unknown., Objective: We assessed peritoneal and myocardial inflammation in the setting of low WBC HIF-1alpha expression through bone marrow transplantation of hematopoietic stem cells transfected with scramble or HIF-1alpha small interfering (si)RNA., Methods and Results: Rosa hematopoietic stem cells (lin(-), cKit(+)) were transfected with a green fluorescent protein (GFP) reporter lentivirus encoding a siRNA to HIF-1alpha or scramble. Irradiated 6- to 8-week-old C57/BL6J mice received 50 000 GFP(+) HIF-1alpha or scramble siRNA-transfected hematopoietic stem cells. Peritonitis or myocardial infarction via left anterior descending coronary artery ligation was induced 6 weeks after bone marrow transplantation. In the peritonitis model, HIF-1alpha siRNA group exhibited a significant decrease in neutrophil and monocyte entry to the peritoneum compared to scramble mice. Similarly neutrophil infiltration into the infarct zone was decreased in the HIF-1alpha siRNA group. No difference of myocardial infarct size was observed between groups. Interestingly, the ejection fraction were similar in both groups at baseline and 3 days post-MI but increased significantly in the HIF-1alpha siRNA group compared to control beginning 7 days after MI. Gene array studies demonstrated that downregulation of WBC HIF-1alpha was associated with decreased WBC CCR1, -2, and -4 expression. Chemotaxis assay results confirmed that decreased monocyte migration induced by downregulation of HIF-1alpha was partially reversed by overexpression of CCR2., Conclusions: Downregulation of leukocyte HIF-1alpha expression resulted in decreased recruitment of WBC to the sites of inflammation and improvement in cardiac function following MI. Downregulation of HIF-1alpha suppressed WBC cytokine receptors CCR1, -2, and -4, which are necessary for WBC mobilization and recruitment to inflammatory cytokines following MI. The effects of downregulation of leukocyte HIF-1alpha on WBC migration are attributable, at least in part, to the decreased CCR2 expression. These results demonstrate that WBC infiltration into the newly injured myocardium plays a significant role in left ventricular remodeling, but not infarct size.

Vibration-induced white finger (VWF) is a disorder seen in workers exposed to hand-transmitted vibration, and is characterized by cold-induced vasospasms and finger blanching. Because overweight people with metabolic syndrome are pre-disposed to developing peripheral vascular disorders, it has been suggested that they also may be at greater risk of developing VWF if exposed to occupational vibration. We used an animal model of metabolic syndrome, the obese Zucker rat, to determine if metabolic syndrome alters vascular responses to vibration. Tails of lean and obese Zucker rats were exposed to vibration (125 Hz, 49 m/s(2) r.m.s.) or control conditions for 4 h/d for 10 d. Ventral tail arteries were collected and assessed for changes in gene expression, levels of reactive oxygen species (ROS) and for responsiveness to vasomodulating factors. Vibration exposure generally reduced the sensitivity of arteries to acetylcholine (ACh)-induced vasodilation. This decrease in sensitivity was most apparent in obese rats. Vibration also induced reductions in vascular nitric oxide concentrations and increases in vascular concentrations of ROS in obese rats. These results indicate that vibration interferes with endothelial-mediated vasodilation, and that metabolic syndrome exacerbates these effects. These findings are consistent with idea that workers with metabolic syndrome have an increased risk of developing VWF.

We report a rare case of gastric collision tumour composed of poorly differentiated adenocarcinoma and neuroendocrine carcinoma in a 56-year-old Caucasian male. The tumour was located in the gastric body and, to our knowledge, it is the tenth case described in the literature and the first in Poland. The adenocarcinoma component constituted 20% of the lesion and was in a more advanced stage than the neuroendocrine component. Additionally, the adenocarcinoma was the only one to metastasize to regional lymph nodes and the liver. The controversies regarding nomenclature of such lesions are discussed and a review of the literature is presented.

Stem cell transplantation at the time of acute myocardial infarction (AMI) improves cardiac function. Whether the improved cardiac function results from regeneration of cardiac myocytes, modulation of remodeling, or preservation of injured tissue through paracrine mechanisms is actively debated. Because no specific stem cell population has been shown to be optimal, we investigated whether the benefit of stem cell transplantation could be attributed to a trophic effect on injured myocardium. Mesenchymal stem cells secrete SDF-1 and the interaction of SDF-1 with its receptor, CXCR4, increases survival of progenitor cells. Therefore, we compared the effects of MSC and MSC engineered to overexpress SDF-1 on cardiac function after AMI. Tail vein infusion of syngeneic MSC and MSC:SDF-1 1 day after AMI in the Lewis rat led to improved cardiac function by echocardiography by 70.7% and 238.8%, respectively, compared with saline controls 5 wk later. The beneficial effects of MSC and MSC:SDF-1 transplantation were mediated primarily through preservation, not regeneration of cardiac myocytes within the infarct zone. The direct effect of SDF-1 on cardiac myocytes was due to the observation that, between 24 and 48 h after AMI, SDF-1-expressing MSC increased cardiac myocyte survival, vascular density (18.2+/-4.0 vs. 7.6+/-2.3 vessels/mm2, P<0.01; SDF-1:MSC vs. MSC), and cardiac myosin-positive area (MSC: 49.5%; mSC:SDF-1: 162.1%) within the infarct zone. There was no evidence of cardiac regeneration by the infused MSC or endogenous cardiac stem cells based on lack of evidence for cardiac myocytes being derived from replicating cells. These results indicate that stem cell transplantation may have significant beneficial effects on injured organ function independent of tissue regeneration and identify SDF-1:CXCR4 binding as a novel target for myocardial preservation.

Recent loss-of-function studies highlight the importance of the transcription factor GATA4 in the myocardial response to injury in the adult heart. However, the potential effects of gain-in-function of GATA4 overexpression, and transcription factors in general, is hindered by the fact that transcription factors are neither secreted nor taken up by cells. Chimeric proteins incorporating motifs of cell-penetrating proteins are secreted from cells and internalized by surrounding cells. We engineered a chimeric protein consisting of GATA4 and the cell-penetrating protein VP22. Cardiac fibroblasts stably transfected with the GATA4:VP22, GFP:VP22, or green fluorescent protein (GFP) constructs were transplanted into Lewis rats 1 month after left anterior descending ligation. GATA4:VP22 expression in the border zone was associated with increased cardiac myosin expression and cardiac myocyte size (30 mum versus 19 mum, P<0.01). Compared with the GFP:VP22 control group, 6 weeks after cardiac fibroblast transplantation (10 weeks after myocardial infarction), animals that received GATA4:VP22-expressing cardiac fibroblasts demonstrated increased cardiac function and less negative remodeling. These data demonstrate a novel strategy for transcription factor delivery to injured myocardium and indicate that the delivery of GATA4 locally to the infarct border zone induces multiple local effects in the border zone cardiac myocytes resulting in beneficial ventricular remodeling and improved global left ventricular function.

MSCs have received attention for their therapeutic potential in a number of disease states, including bone formation, diabetes, stem cell engraftment after marrow transplantation, graft-versus-host disease, and heart failure. Despite this diverse interest, the molecular signals regulating MSC trafficking to sites of injury are unclear. MSCs are known to transiently home to the freshly infarcted myocardium. To identify MSC homing factors, we determined chemokine expression pattern as a function of time after myocardial infarction (MI). We merged these profiles with chemokine receptors expressed on MSCs but not cardiac fibroblasts, which do not home after MI. This analysis identified monocyte chemotactic protein-3 (MCP-3) as a potential MSC homing factor. Overexpression of MCP-3 1 month after MI restored MSC homing to the heart. After serial infusions of MSCs, cardiac function improved in MCP-3-expressing hearts (88.7%, p < .001) but not in control hearts (8.6%, p = .47). MSC engraftment was not associated with differentiation into cardiac myocytes. Rather, MSC engraftment appeared to result in recruitment of myofibroblasts and remodeling of the collagen matrix. These data indicate that MCP-3 is an MSC homing factor; local overexpression of MCP-3 recruits MSCs to sites of injured tissue and improves cardiac remodeling independent of cardiac myocyte regeneration.