Campylobacter jejuni is the leading cause of bacterial foodborne illness in the world, with symptoms ranging from acute diarrhea to severe neurological disorders. Contaminated poultry meat is a major ...source of C. jejuni infection, and therefore, strategies to reduce this organism in poultry, are expected to reduce the incidence of Campylobacter-associated diseases. We have investigated whether oral administration of C. jejuni-specific single-domain antibodies would reduce bacterial colonization levels in chickens. Llama single-domain antibodies specific for C. jejuni were isolated from a phage display library generated from the heavy chain IgG variable domain repertoire of a llama immunized with C. jejuni flagella. Two flagella-specific single-domain antibodies were pentamerized to yield high avidity antibodies capable of multivalent binding to the target antigen. When administered orally to C. jejuni-infected two-day old chicks, the pentabodies significantly reduced C. jejuni colonization in the ceca. In vitro, the motility of the bacteria was also reduced in the presence of the flagella-specific pentabodies, suggesting the mechanism of action is through either direct interference with flagellar motility or antibody-mediated aggregation. Fluorescent microscopy and Western blot analyses revealed specific binding of the anti-flagella pentabodies to the C. jejuni flagellin.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Human papillomavirus (HPV) is the causative agent of cervical cancer (CxCa) and the most commonly sexually transmitted pathogen worldwide. HPV type 16 (HPV-16) E7 oncoprotein is constitutively ...produced in CxCa and considered as a good antigen candidate for the development of new therapeutic CxCa vaccines. Here, we report the use of non-genetically modified, E7-expressing lactic acid bacteria (LAB) by using the cell-binding domain from
Lactobacillus casei
A2 phage lysin as a cell wall anchor. The versatility of this system was validated by investigating E7 stability at the surface of
Lactococcus lactis
and
L. casei
, two major species of LAB. Moreover, we demonstrated the successful use of these LAB displaying E7 antigen as a mucosal live vaccine in mice. Altogether, these results show the feasibility of using non-genetically modified LAB for low-cost mucosal immunotherapy against HPV-related CxCa in humans.
Celotno besedilo
Dostopno za:
CEKLJ, DOBA, EMUNI, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SBMB, SBNM, UILJ, UKNU, UL, UM, UPUK
Key Clinical Message
In patients with acute symptoms such as pain, swelling, and erythema of the upper extremities shortly after receiving COVID‐19 vaccines, even inactivated virus vaccines, these ...symptoms may indicate thrombosis, which may be due to the vaccination.
BBIBP‐CorV COVID‐19 vaccine (Sinopharm vaccine) is an inactivated whole virus vaccine to control the COVID‐19 pandemic. Studies concluded that inactivated COVID‐19 vaccines do not increase the risk of thrombosis. This report presents a 23‐year‐old man with the chief complaint of severe pain, swelling, and erythema of the right upper extremity following his second dose of the Sinopharm vaccine. Duplex ultrasound of the right upper extremity revealed upper extremity deep vein thrombosis, and treatment started with oral anticoagulation. It is probably the first upper extremity deep vein thrombosis case following inactivated COVID‐19 vaccines.
A 6‐year‐old girl with persistent headaches and the visual problem was diagnosed as a delayed onset cranial pansynostosis with concurrent type 1.5 Arnold‐Chiari malformation. She underwent ...multi‐sutural reconstructive surgery and followed. The headache was greatly decreased and tonsillar‐brain stem herniation and syrinx were resolved.
Craniosynostosis surgery can reduce intracranial pressure to a great extent so that concurrent brain stem herniation and syrinx may resolve, gradually. It is important to prioritize the main underlying lesion in such complex cases.
The enteric pathogen,
is a major cause of human gastroenteritis globally and with increasing bacterial resistance to antibiotics, alternative solutions are urgently needed. Single domain antibodies ...(sdAbs), the smallest antibody fragments that retain antigen binding specificity and affinity, are derived from variable heavy-chain only fragments (VHH) of camelid heavy-chain-only immunoglobulins. SdAbs typically contain a single disulfide bond simplifying recombinant protein production in microbial systems. These factors make sdAbs ideally suited for the development of effective anti-bacterial therapeutics. To this end, we generated an anti-Salmonella VHH library from which we screened for high affinity sdAbs. We present a novel sdAb (Abi-Se07) that targets the Salmonella virulence factor, FliC, required for bacterial motility and invasion of host cells. We demonstrate that Abi-Se07 bound FliC with a
of 16.2 ± 0.1 nM. In addition, Abi-Se07 exhibited cross-serovar binding to whole cells of
serovar Typhimurium, Heidelberg, and Hadar. Abi-Se07 significantly inhibited bacterial motility and significantly reduced
colonization in a more native environment of chicken jejunum epithelium. Taken together, we have identified a novel anti-Salmonella sdAb and discuss future efforts toward therapeutic development.
Stem cell sources for regenerative medicine Riazi, Ali M; Kwon, Sarah Y; Stanford, William L
Methods in molecular biology (Clifton, N.J.),
2009, Letnik:
482
Journal Article
Tissue-resident stem cells or primitive progenitors play an integral role in homeostasis of most organ systems. Recent developments in methodologies to isolate and culture embryonic and somatic stem ...cells have many new applications poised for clinical and preclinical trials, which will enable the potential of regenerative medicine to be realized. Here, we overview the current progress in therapeutic applications of various stem cells and discuss technical and social hurdles that must be overcome for their potential to be realized.
Key Clinical Message
Patients complaining of rectal bleeding, constipation, and a suspicious mass in colonoscopy should undergo biopsy. Histological features such as fibromuscular obliteration in the ...lamina propria favor SRUS, a benign disorder.
Solitary rectal ulcer syndrome (SRUS) is a rare benign rectal disorder often misdiagnosed with other diseases, such as IBD, constipation, and malignancies. Therefore, it is necessary to know its diagnostic features and treatment. In this report, we present a case of a polypoid solitary rectal ulcer presented with rectal bleeding and chronic constipation mimicking rectal neoplasm on colonoscopy. Histopathological study showed the characteristics of SRUS, the most important of which was fibromuscular obliteration in the lamina propria.
Introduction: Gastrointestinal (GI) bleeding is the most life-threatening complication of cirrhosis and it's predicting is crucial for the management of cirrhotic patients. The present study aimed to ...assess the relationship between INR and plasma fibrinogen level and the risk of GI bleeding using in cirrhotic patients. Methods: In the present cross-sectional study, seventy-eight cirrhotic patients were enrolled. We assessed demographic, biochemical, hematologic parameters in all patients. Underlying diseases and the etiology of cirrhosis were documented. The Child-Pugh and the Model for End-stage Liver Disease (MELD) scores were used to assess the severity of liver cirrhosis. The history of bleeding episodes within 6 months before inclusion were recorded. A blood sample was drowned and fibrinogen and prothrombin time (PT) were measured and INR was calculated. Results: The patients' mean age was 51.23±15.08 years and 40 (51.3%) were male. About 17 patients (%21.7) had a history of GI bleeding within 6 months before the study. The significant difference was observed between the two groups who experienced bleeding and who did not regarding the fibrinogen level (P < 0.05). The fibrinogen level was a better predictive marker of bleeding in cirrhotic patients (AUC: 0.87). According to the results of predictive tests, the fibrinogen level had a sensitivity of (77%) and specificity of (%94) in the prediction of bleeding with the cut-off value of 182.5. Conclusion: The results of the present study showed that the fibrinogen level is a better predictor of bleeding in cirrhotic patients compared with INR.
Objectives The aim of this study was to examine the function of the bone morphogenic protein growth differentiation factor 5 (Gdf5) in a mouse model of myocardial infarction (MI). Background The Gdf5 ...has been implicated in skeletal development, but a potential role in the heart had not been studied. Methods The Gdf5-knockout (KO) and wild-type (WT) mice were subjected to permanent left anterior descending coronary artery (LAD) ligation. Cardiac pathology, function, gene expression levels, and signaling pathways downstream of Gdf5 were examined. Effects of recombinant Gdf5 (rGdf5) were tested in primary cardiac cell cultures. Results The WT mice showed increased cardiac Gdf5 levels after MI, with increased expression in peri-infarct cardiomyocytes and myofibroblasts. At 1 and 7 days after MI, no differences were observed in ischemic or infarct areas between WT and Gdf5-KO mice. However, by 28 days after MI, Gdf5-KO mice exhibited increased infarct scar expansion and thinning with decreased arteriolar density compared with WT. The Gdf5-KO hearts also displayed increased left ventricular dilation, with decreased contractility after MI. At 4 days after MI, Gdf5-KO mice exhibited increased cardiomyocyte apoptosis and decreased expression of anti-apoptotic genes Bcl2 and Bcl-xL compared with WT. Unexpectedly, Gdf5-KO hearts displayed increased Smad 1/5/8 phosphorylation but decreased p38-mitogen-activated protein kinase (MAPK) phosphorylation versus WT. The latter was associated with increased collagen gene (Col1a1, Col3a1) expression and fibrosis. In cultures, rGdf5 induced p38-MAPK phosphorylation in cardiac fibroblasts and Smad-dependent increases in Bcl2 and Bcl-xL in cardiomyocytes. Conclusions Increased expression of Gdf5 after MI limits infarct scar expansion in vivo. These effects might be mediated by Gdf5-induced p38-MAPK signaling in fibroblasts and Gdf5-driven Smad-dependent pro-survival signaling in cardiomyocytes.
Introduction
: Considering that portal hypertension is principally caused by hepatic fibrosis, some studies postulated the predictive value of serum liver fibrosis indices in the diagnosis of portal ...hypertension. In this study we assessed the prognostic value of serum indices in the diagnosis of portal hypertension in cirrhotic patients.
Methods
: One hundred two cirrhotic patients were selected according to inclusion/exclusion criteria. Cirrhosis and the Child-Pugh score was determined by the gastroenterologist. Portal hypertension was diagnosed by the radiologist using the color Doppler method. The fasting blood sample was drawn and different serum indices were determined. The following indices were calculated: FIB4, Fibroindex, APRI, FORNS, LOK.
Results
: The patients mean age was 54.39±6.60 years. About 52.94% of the patients were women. The mean liver enzymes level was higher in patients with portal hypertension. In 50.98% of patients, the etiology of cirrhosis was viral hepatitis. Significant differences was observed between the two groups regarding the studied indices (P<0.05). According to the results of the ROC curve, the FORNS index was a better predictive marker of portal hypertension in cirrhotic patients. The maximum AUC (area under the curve) was for the FORNS index. According to the results of diagnostic tests, the FORNS index had adequate sensitivity and specificity in the diagnosis of portal hypertension with the cut-off value of 8.51.
Conclusion
: The results of the present study showed that the FORNS index is a better predictor of portal hypertension in cirrhotic patients.