Transcriptome Analysis of Signaling Pathways in Caco-2 Cells Involved in the Formation of Intestinal Villi

xlomafota.13 shared this article with you from Inoreader Transcriptome Analysis of Signaling Pathways in Caco-2 Cells Involved in the Formation of Intestinal Villi Via Latest Results for Applied Biochemistry and Microbiology Abstract Caco-2 cells are traditionally used to construct in vitro models of the intestinal barrier. One characteristic of the mature intestine is the presence of villi—connective tissue outgrowths covered with epithelial cells. It was recently shown that Caco-2 cells form structures resembling intestinal villi during prolonged cultivation. In this work, we showed via transcriptome analysis that the BMP and PDGF signaling cascades involved in the formation of villi in vivo are significantly altered during the differentiation of Caco-2 cells and, therefore, can participate in the formation of similar structures in vitro. In particular, we found a significant decrease in the expression of the BMP4, BMP7, and BMP8A genes in differentiated cells as compared to undifferentiated cells. We also first discovered periodic fluctuations in transepithelial resistance upon the differentiation of Caco-2 cells. The period of observed fluctuations indicates that they can occur as a result of cell proliferation during villus formation. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Properties and Biotechnological Application of Mutant Derivatives of the Mini-Intein PRP8 from Penicillium chrysogenu m with Improved Control of C-Terminal Processing

xlomafota.13 shared this article with you from Inoreader Properties and Biotechnological Application of Mutant Derivatives of the Mini-Intein PRP8 from Penicillium chrysogenu m with Improved Control of C-Terminal Processing Via Latest Results for Applied Biochemistry and Microbiology Abstract Mutant variants of mini-intein PRP8 from Penicillium chrysogenum (Int4b) with improved control of C-terminal processing are characterized. The studied variants can serve as the basis for the self-removal of polypeptide tags that can carry an affine label and optimize the process of the obtainment of target proteins and peptides in E. coli cells. They make it possible to synthesize target molecules composed of soluble and insoluble hybrid proteins (fusions), to conduct their affine purification and autocatalytic processing, and to obtain mature target products. The presented variants have a number of features as compared to the known prototypes. In particular, the mutant mini-intein Int4bPRO, which contains the L93P mutation, has temperature-dependent properties. It is able to produce target molecules composed of soluble fusions at a cultivation temperature below 30°C; however, it directs most synthesized fusions into insoluble intracellular aggregates after an increase in temperature to 37°C. The transition of Int4bPRO to an insoluble form is accompanied by the complete inactivation of C-terminal processing. Further application of the standard protein denaturation–renaturation procedures enables efficient reactivation of Int4bPRO and the processing of its fusions in vitro. Two other variants, Int4b56 and Int4b36, which contain the point mutation T62N or a combination of D144N and L146T mutations, respectively, have a reduced rate of C-terminal processing. Their use in E. coli cells allows optimization of the biosynthesis of biologically active target proteins and peptides composed of soluble fusions that are suitable for affine purification and subsequent intein-dependent processing without the use of protein denaturation–renaturation procedures. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation

xlomafota.13 shared this article with you from Inoreader Clusterin ameliorates tau pathology in vivo by inhibiting fibril formation Via Latest Results for Acta Neuropathologica Communications Abstract The molecular chaperone Clusterin (CLU) impacts the amyloid pathway in Alzheimer's disease (AD) but its role in tau pathology is unknown. We observed CLU co-localization with tau aggregates in AD and primary tauopathies and CLU levels were upregulated in response to tau accumulation. To further elucidate the effect of CLU on tau pathology, we utilized a gene delivery approach in CLU knock-out (CLU KO) mice to drive expression of tau bearing the P301L mutation. We found that loss of CLU was associated with exacerbated tau pathology and anxiety-like behaviors in our mouse model of tauopathy. Additionally, we found that CLU dramatically inhibited tau fibrilization using an in vitro assay. Together, these results demonstrate that CLU plays a major role in both amyloid and tau pathologies in AD. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cerebral organoids: emerging ex vivo humanoid models of glioblastoma

xlomafota.13 shared this article with you from Inoreader Cerebral organoids: emerging ex vivo humanoid models of glioblastoma Via Latest Results for Acta Neuropathologica Communications Abstract Glioblastoma is an aggressive form of brain cancer that has seen only marginal improvements in its bleak survival outlook of 12–15 months over the last forty years. There is therefore an urgent need for the development of advanced drug screening platforms and systems that can better recapitulate glioblastoma's infiltrative biology, a process largely responsible for its relentless propensity for recurrence and progression. Recent advances in stem cell biology have allowed the generation of artificial tridimensional brain-like tissue termed cerebral organoids. In addition to their potential to model brain development, these reagents are providing much needed synthetic humanoid scaffolds to model glioblastoma's infiltrative capacity in a faithful and scalable manner. Here, we highlight and review the early breakthroughs in this growing field and discuss its potential future role for glioblastoma research. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Successful conversion surgery of distal pancreatectomy with celiac axis resection (DP-CAR) with double arterial reconstruction using saphenous vein grafting for locally advanced pancreatic cancer: a case report

xlomafota.13 shared this article with you from Inoreader Successful conversion surgery of distal pancreatectomy with celiac axis resection (DP-CAR) with double arterial reconstruction using saphenous vein grafting for locally advanced pancreatic cancer: a case report Via Latest Results for Surgical Case Reports Abstract Background Pancreatic cancer is a disease with a poor prognosis, requiring multidisciplinary treatment combining chemotherapy and surgery for effective management. Distal pancreatectomy with celiac axis resection (DP-CAR) is a surgical intervention performed for locally advanced pancreatic cancer, but the benefit of arterial reconstruction in DP-CAR is unclear. Case presentation A 49-year-old man with pancreatic cancer was referred to our hospital. Imaging revealed a 54-mm tumor mainly in the pancreatic body, but with arterial infiltration including into the celiac, common hepatic, left gastric, splenic and gastroduodenal arteries. Distant metastases were not detected. The patient was diagnosed with unresectable locally advanced pancreatic cancer and chemoradiotherapy was planned. Three cycles of gemcitabine (1000 mg/m2) plus nab-paclitaxel (125 mg/m2) every 4 weeks were followed by irradiation (2 Gy/day, total 50 Gy over 25 days) together with S-1 administration (80 mg/m2/day). A partial response (PR) according to Response Evaluation Criteria in Solid Tumors (RECIST) was achieved, so surgical intervention was considered. Because the tumor had invaded the root of the gastroduodenal artery, we performed DP-CAR with resection of the gastroduodenal artery, followed by a rterial reconstruction of the proper hepatic and left gastric arteries, anastomosed with the abdominal aorta using a great saphenous vein graft in the shape of a "Y". Histopathology showed that 60% of tumor cells were destroyed by the chemoradiotherapy, defined as grade IIb in the Evans classification. No malignancy was detected at the surgical margin, including the celiac artery, gastroduodenal artery or pancreatic stump; thus R0 surgery was successful. S-1 (80 mg/day) was administered as adjuvant chemotherapy for 6 months. The patient is now doing well without recurrence for > 2 years after the initial treatment (more than 16 months after surgery). Conclusion For locally advanced pancreatic cancer, multidisciplinary treatment combining gemcitabine/nab-paclitaxel-based chemoradiotherapy and then DP-CAR surgery with gastroduodenal artery resection and arterial reconstruction using saphenous vein grafting enabled R0 resection in this patient and led to a favorable long-term prognosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Beta- and Novel Delta-Coronaviruses

xlomafota.13 shared this article with you from Inoreader Beta- and Novel Delta-Coronaviruses Are Identified from Wild Animals in the Qinghai-Tibetan Plateau, China Via Latest Results for Virologica Sinica Abstract Outbreaks of severe virus infections with the potential to cause global pandemics are increasingly concerning. One type of those commonly emerging and re-emerging pathogens are coronaviruses (SARS-CoV, MERS-CoV and SARS-CoV-2). Wild animals are hosts of different coronaviruses with the potential risk of cross-species transmission. However, little is known about the reservoir and host of coronaviruses in wild animals in Qinghai Province, where has the greatest biodiversity among the world's high-altitude regions. Here, from the next-generation sequencing data, we obtained a known beta-coronavirus (beta-CoV) genome and a novel delta-coronavirus (delta-CoV) genome from faecal samples of 29 marmots, 50 rats and 25 birds in Yushu Tibetan Autonomous Prefecture, Qinghai Province, China in July 2019. According to the phylogenetic analysis, the beta-CoV shared high nucleotide identity with Coronavirus HKU24. Although the novel delta-CoV (MtCoV) was closely related to Sp arrow deltacoronavirus ISU42824, the protein spike of the novel delta-CoV showed highest amino acid identity to Sparrow coronavirus HKU17 (73.1%). Interestingly, our results identified a novel host (Montifringilla taczanowskii) for the novel delta-CoV and the potential cross-species transmission. The most recent common ancestor (tMRCA) of MtCoVs along with other closest members of the species of Coronavirus HKU15 was estimated to be 289 years ago. Thus, this study increases our understanding of the genetic diversity of beta-CoVs and delta-CoVs, and also provides a new perspective of the coronavirus hosts. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Outcomes of tissue reconstruction in distal lower leg fractures

xlomafota.13 shared this article with you from Inoreader Outcomes of tissue reconstruction in distal lower leg fractures: a retrospective cohort study Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Open and closed fractures can be associated with posttraumatic or postoperative soft tissue defects caused by initial trauma, operative procedures, or infections. This study evaluated the postoperative outcomes in patients with open or closed lower leg fractures, related soft tissue defects, and subsequent flap coverage. Methods We performed a retrospective single-center cohort study in a level 1 trauma center. We analyzed the patients treated from January 2012 through December 2017 and recorded demographics, treatment, and outcome data. The outcome data were measured via patient-reported Foot and Ankle Outcomes Scores (FAOS) and EQ-5D-5L scores. Results We included 22 patients with complicated fractures (11 open and 11 closed) and subsequent soft tissue defects and flap coverages. The mean follow-up time was 41.2 months. Twenty-one patients developed infections, and necrosis at the site of surgery manifested in all closed fractures. Therefore, all patients needed soft tissue reconstructions. Preoperatively, 16 patients underwent arterial examinations via angiography and six underwent ultrasound examinations of the venous system. Ten patients had complications involving the flaps due to ischemia and consequent necrosis. The mean EQ-5D index was 0.62 ± 0.27, and EQ-5D VAS score was 57.7 ± 20.2. The mean FAOS was 60.7 ± 22.2; in particular, quality of life was 32.3 ± 28.8. The rate of returning to work in our patient group was 37.5% after 1 year. Conclusions Distal tibial fractures often require revisions and soft tissue reconstruction. The evaluated patient population had poor outcomes in terms of function, quality of life, and return to work. Furthermore, patients suffering from flap ischemia have worse outcomes than those without flap ischemia. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prevalence and predictors of work-related musculoskeletal disorders among workers of a gold mine in south Kivu, Democratic Republic of Congo

xlomafota.13 shared this article with you from Inoreader Prevalence and predictors of work-related musculoskeletal disorders among workers of a gold mine in south Kivu, Democratic Republic of Congo Via Latest Results for BMC Musculoskeletal Disorders Abstract Background Work-related musculoskeletal disorders (WRMSDs) are a major constraint to worker performance and health. However, research on their prevalence and associated factors among workers at gold mines in the Democratic Republic of Congo (DRC) is insufficient. The present study aimed to determine the prevalence and predictors of WRMSDs among workers of a Gold Mine in South Kivu, DRC. Methods Cross sectional data on prevalence of WRMSDs and risk factors was collected using a modified Nordic questionnaire and upper limb Core QX checklist from 196 workers of a gold mine. WRMSDs were defined as pain or injury(ies) or discomfort, numbness or limitation of movement in the musculoskeletal system at any time in the past 12 months which lasted at least 24 h. These had to be either induced or aggravated by work and circumstances of its performance. A generalised linear model of the Poison family with link log and robust error variances was used to generate prevalence ratios (PRs) and 95% confidence intervals (CIs) for the factors associated with WRMSDs. The effect of individual, ergonomic and psychosocial factors on WRMSDs were investigated while controlling for known confounders. Results Most workers were males 187 (95.4%) and their age ranged between 23 and 60 years with mean of 36.3 years. Of the 196 workers, 49 (25.0%) reported having at least one WRMSD during the previous 12 months. WRMSDs with highest occurrence rate were the lower back pain (14.8%), followed by thighs/hip pain (9.2%) and shoulder pain (8.2%). Prolonged heavy lifting/shovelling shovelling (PR = 1.69, 95% CI [1.32, 3.24] and longer work shifts (> 9 h) (PR = 3.56, 95% CI [1.76, 16.58]) were predictive for WRMSDs while jobs with low demands were protective against WRMSDs (PR = 0.18, 95% CI [0.08, 0.44]). Conclusion The prevalence of WRMSDs is high and associated with prolonged heavy lifting/shovelling, longer work shifts and job demands. We recommend lowering workload and job demands and improving work ergonomics to mitigate and prevent the WRMSDs among workers in goldmines. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later

xlomafota.13 shared this article with you from Inoreader Higher aggrecan 1-F21 epitope concentration in synovial fluid early after anterior cruciate ligament injury is associated with worse knee cartilage quality assessed by gadolinium enhanced magnetic resonance imaging 20 years later Via Latest Results for BMC Musculoskeletal Disorders Abstract Background To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury. Methods We studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples. Results Western blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between − 0.67 and − 1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values. Conclusion Higher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hybrid-Therapie eines Dysphagia-lusoria-Rezidives mittels thorakalem Stentgraft und Transposition der A. subclavia

xlomafota.13 shared this article with you from Inoreader Hybrid-Therapie eines Dysphagia-lusoria-Rezidives mittels thorakalem Stentgraft und Transposition der A. subclavia Via Latest Results for Gefässchirurgie View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Besteht ein Zusammenhang zwischen der peripheren arteriellen Verschlusskrankheit und Parodontitis?

xlomafota.13 shared this article with you from Inoreader Besteht ein Zusammenhang zwischen der peripheren arteriellen Verschlusskrankheit und Parodontitis? Via Latest Results for Gefässchirurgie Zusammenfassung Die periphere arterielle Verschlusskrankheit (PAVK) ist die häufigste Durchblutungsstörung peripherer Gefäße. Die PAVK wird durch Risikofaktoren und Komorbiditäten, wie zum Beispiel Rauchen, Bluthochdruck, Dyslipidämie, Diabetes und chronische Niereninsuffizienz begünstigt. Epidemiologische Studien weisen allerdings auch darauf hin, dass zusätzlich die Parodontitis (PA) das Risiko für eine PAVK erhöhen kann. Die PA ist eine häufige, durch bakteriellen Biofilm ausgelöste, chronische Entzündung des Zahnhalteapparates. Parodontitis wird durch mangelhafte Mundhygiene, Rauchen und Diabetes begünstigt und die Prävalenz steigt mit dem Alter an. Beide Erkrankungen bzw. deren Symptome sind therapierbar, wenn die Behandlung frühzeitig einsetzt. Deshalb ist die Früherkennung besonders wichtig. Obwohl der Nachweis einer kausalen Rolle der PA für die Entstehung der PAVK noch aussteht, unterstützen die in diesem Artikel zusammengefassten Daten den Vorschla g einer interdisziplinären Zusammenarbeit zwischen Gefäß- und Zahnmedizinern. Es kann in der gefäßmedizinischen Praxis erwogen werden, PAVK-Patienten, unabhängig vom Stadium ihrer Erkrankung, zwecks Diagnose und Behandlung einer PA an Zahnärzt*innen zu verweisen. Umgekehrt sollten auch Zahnärzt*innen erwägen, Patienten, die an einer schweren Form der PA leiden, an Gefäßmediziner zu verweisen. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Infektionen in der Shuntchirurgie

xlomafota.13 shared this article with you from Inoreader Infektionen in der Shuntchirurgie Via Latest Results for Gefässchirurgie Zusammenfassung Infektionen im Bereich eines Hämodialysezugangs stellen die zweithäufigste Komplikation nach der Thrombose dar, bei Vorhofkathetern sind Infektionen gar die häufigste Komplikation. Diese Infekte bedrohen sowohl den Dialysezugang selbst als auch das Leben der Patienten, da Zugangsinfektionen die Mortalität des Patientenkollektivs dramatisch erhöhen. Neben der allgemeinen Infektdiagnostik kommt der Sonographie und der frühen Blutkulturentnahme eine besondere Bedeutung für die weitere Therapieplanung zu. Unkomplizierte Infektionen nativer Fisteln können oft ambulant mit peroraler Antibiotikagabe erfolgreich therapiert werden, Abszesse müssen chirurgisch drainiert werden. Bei perianastomotischen Infekten besteht das Hauptrisiko in einer septischen Arrosionsblutung, sodass hier eine dringliche Operationsindikation besteht. Prothetische Hämodialysezugänge können je nach Ausdehnung des Infekts als segmentale oder subtotale Graftexplantation, nach Möglichkeit mit prothetischem Ersatz über nicht vom Infekt tangierten Arealen (aseptischer Bypass) chirurgisch therapiert werden. Bei vollständigem Protheseninfekt muss das prothetische Material in toto entfernt werden. Vorhofkatheterinfekte sollten stadiengerecht behandelt werden, obligat sind hier zentrale und periphere Blutkulturentnahmen. Der unkomplizierte Infekt des Exits kann bei negativer Blutkultur rein antibiotisch therapiert werden. Abszessbildungen im subkutanen Tunnel erfordern einen Katheterwechsel nach kontralateral, sofern keine Bakteriämie besteht. Bakteriäme Formen des Vorhofkatheterinfekts erfordern die dringliche Explantation des Vorhofkatheters und eine Neuanlage nach negativen Blutkulturen. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.