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Σάββατο 14 Ιουλίου 2018

Prevalence and Characterization of Staphylococcus aureus Cultured From Raw Milk Taken From Dairy Cows With Mastitis in Beijing, China.

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Prevalence and Characterization of Staphylococcus aureus Cultured From Raw Milk Taken From Dairy Cows With Mastitis in Beijing, China.

Front Microbiol. 2018;9:1123

Authors: Wang W, Lin X, Jiang T, Peng Z, Xu J, Yi L, Li F, Fanning S, Baloch Z

Abstract
The colonization of dairy herds and subsequent contamination of raw milk by Staphylococcus aureus (S. aureus), especially those expressing a multi-drug resistance (MDR), biofilm and toxins producing ability, remains an important issue for both the dairy producer and public health. In this study, we investigated the prevalence, antimicrobial resistance, virulence, and genetic diversity of S. aureus in raw milk taken from 2 dairy farms in Beijing, China. Ninety (46.2%, 90/195) samples were positive for S. aureus. Resistant to penicillin (PEN) (31.3%), ciprofloxacin (18.8%) and enrofloxacin (15.6%) were the most often observed. Isolates cultured from farm B showed significantly higher resistance to penicillin (73.9%), ciprofloxacin (34.8%), enrofloxacin (34.8%), tilmicosin (17.4%), and erythromycin (17.4%) than those from farm A (p < 0.05). Totally, 94.8% S. aureus harbored at least one virulence gene and the pvl (93.8%), sec (65.6%), and sea (60.4%) genes were the most frequently detected. The pvl and sec genes were more often detected in isolates from farm A (97.3% and 84.9% respectively) than those from farm B (p < 0.05). Of all 77 staphylococcus enterotoxin (SE)-positive isolates, more than 90% could produce enterotoxins and 70.1% could produce two types. Biofilm related genes (icaA/D, clf/B, can, and fnbA) were detected in all96 isolates. All 96 isolates could produce biofilm with 8.3, 70.8, and 18.8% of the isolates demonstrating weak, moderate and strong biofilm formation, respectively. A total of 5 STs, 7 spa types (1 novel spa type t17182), 3agr types (no agrII), and 14 SmaI-pulso-types were found in this study. PFGE cluster II-CC1-ST1-t127-agr III was the most prevalent clone (56.3%). Isolates of agr III (PFGE Cluster I/II-CC1-ST1-t127/2279) had higher detection of virulence genes than those of agr I and agr IV. TheMSSA-ST398-t1456-agr I clone expressed the greatest MDRbut with no virulence genes and weakly biofilm formation. Our finding indicated a relatively high prevalence of S. aureus with less antimicrobial resistance but often positive for enterotoxigenicity and biofilm formation. This study could help identify predominant clones and provide surveillance measures to eliminate and decrease the contamination of S. aureus in raw milk of dairy cows with mastitis.

PMID: 29988423 [PubMed]

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Staphylococcus aureus Evasion of Host Immunity in the Setting of Prosthetic Joint Infection: Biofilm and Beyond.

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Staphylococcus aureus Evasion of Host Immunity in the Setting of Prosthetic Joint Infection: Biofilm and Beyond.

Curr Rev Musculoskelet Med. 2018 Jul 09;:

Authors: Ricciardi BF, Muthukrishnan G, Masters E, Ninomiya M, Lee CC, Schwarz EM

Abstract
PURPOSE OF REVIEW: The incidence of complications from prosthetic joint infection (PJI) is increasing, and treatment failure remains high. We review the current literature with a focus on Staphylococcus aureus pathogenesis and biofilm, as well as treatment challenges, and novel therapeutic strategies.
RECENT FINDINGS: S. aureus biofilm creates a favorable environment that increases antibiotic resistance, impairs host immunity, and increases tolerance to nutritional deprivation. Secreted proteins from bacterial cells within the biofilm and the quorum-sensing agr system contribute to immune evasion. Additional immunoevasive properties of S. aureus include the formation of staphylococcal abscess communities (SACs) and canalicular invasion. Novel approaches to target biofilm and increase resistance to implant colonization include novel antibiotic therapy, immunotherapy, and local implant treatments. Challenges remain given the diverse mechanisms developed by S. aureus to alter the host immune responses. Further understanding of these processes should provide novel therapeutic mechanisms to enhance eradication after PJI.

PMID: 29987645 [PubMed - as supplied by publisher]

https://ift.tt/2NSesYX

A Dual-Replicon Shuttle Vector System for Heterologous Gene Expression in a Broad Range of Gram-Positive and Gram-Negative Bacteria.

A Dual-Replicon Shuttle Vector System for Heterologous Gene Expression in a Broad Range of Gram-Positive and Gram-Negative Bacteria.

Curr Microbiol. 2018 Jul 09;:

Authors: Hua M, Guo J, Li M, Chen C, Zhang Y, Song C, Jiang D, Du P, Zeng H

Abstract
Origin of replication (ori in theta-replicating plasmids or dso in rolling circle replicating plasmids) initiates plasmid replication in a broad range of bacteria. These two kinds of plasmids were both identified in Streptococcus, a genus composed of both human commensal bacteria and pathogens with the ability to cause severe community-acquired infections, including meningitides, septicemia, and respiratory tract diseases. Given the important roles of Streptococcus in the exchange of genetic elements with other symbiotic microbes, the genotypes and phenotypes of both Streptococcus spp. and other symbiotic species could be changed during colonization of the host. Therefore, an improved plasmid system is required to study the functional, complicated, and changeable genomes of Streptococcus. In this study, a dual-replicon shuttle vector system named pDRE was constructed to achieve heterologous gene expression. The vector system contained theta replicon for Escherichia coli. The origin of rolling circle replicon was synthesized according to pMV158 in Gram-positive bacteria. By measuring the products of inserted genes at multiple cloning sites, the ability of this vector system in the replication and expression of heterologous genes was assessed in four Streptococcus and three other Gram-positive bacteria: Bacillus subtilis, Lactococcus lactis, and Staphylococcus aureus. The results showed that the newly constructed vector could simultaneously replicate and express heterologous genes in a broad range of Gram-positive and Gram-negative bacteria, thus providing a potentially powerful genetic tool for further functional analysis.

PMID: 29987521 [PubMed - as supplied by publisher]

https://ift.tt/2JmbOr6

WGS analysis of ST9-MRSA-XII isolates from live pigs in China provides insights into transmission among porcine, human and bovine hosts.

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WGS analysis of ST9-MRSA-XII isolates from live pigs in China provides insights into transmission among porcine, human and bovine hosts.

J Antimicrob Chemother. 2018 Jul 06;:

Authors: Zhou W, Li X, Osmundson T, Shi L, Ren J, Yan H

Abstract
Objectives: To elucidate the phylogenetic relationships among ST9-MRSA-XII isolates from different sources and their genetic features in colonization of different hosts.
Methods: We obtained whole-genome sequences of two ST9-MRSA-XII isolates from nasal swabs associated with live pigs in China, and compared them with 135 previously sequenced genomes of 78 human-associated, 39 bovine and 18 porcine Staphylococcus aureus consisting of 11 MRSA of SCCmecXII, 62 MRSA of other SCCmec types and 62 MSSA. The distribution of diverse mobile genetic elements (MGEs), resistance genes and virulence determinants was investigated in relation to isolate phylogeny. Comparisons of SNPs and small insertion/deletions (indels) were conducted to examine genome-level variation between porcine and bovine ST9-MRSA-XII.
Results: Phylogenetic analysis revealed that both of our porcine ST9-MRSA-XII isolates clustered with porcine, bovine and human-associated ST9-MRSA-XII. All of these isolates possessed a novel type V pathogenicity island, νSaα, carrying the von Willebrand-binding protein gene vwb, the immune evasion complex gene scn, the aminoglycoside resistance gene aadE, staphylococcal superantigen-like genes (ssl1-ssl11) and lpl tandem genes. Compared with bovine ST9-MRSA-XII BA01611, our porcine isolates contain non-synonymous nucleotide substitutions in genes encoding adhesins and an indel located in a phosphonate ABC transporter pseudogene.
Conclusions: The data suggest transmission of ST9-MRSA-XII among swine, cattle and humans. The extraordinary success of the ST9-MRSA-XII group in colonization of various hosts is likely due to acquisition of many MGEs harbouring functional antimicrobial resistance and virulence genes. Transmission of ST9-MRSA-XII between porcine and bovine hosts was accompanied by changes in binding profile and function in genes involved in metabolism.

PMID: 29986036 [PubMed - as supplied by publisher]

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Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) among employees and in the environment of a small animal hospital.

https:--linkinghub.elsevier.com-ihub-ima

Methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) among employees and in the environment of a small animal hospital.

Vet Microbiol. 2018 Jul;221:153-158

Authors: Feßler AT, Schuenemann R, Kadlec K, Hensel V, Brombach J, Murugaiyan J, Oechtering G, Burgener IA, Schwarz S

Abstract
The aim of the study was to investigate methicillin-resistant Staphylococcus aureus (MRSA) and methicillin-resistant Staphylococcus pseudintermedius (MRSP) among employees of a small animal hospital and the hospital environment. In total, 96 swabs from employees and 73 swabs from the clinic environment were investigated. Cation-adjusted-Mueller-Hinton broth (CAMHB) + 6.5% NaCl was used for enrichment before plating on Mueller-Hinton (MH) agar with 2% NaCl and 0.25 mg/L oxacillin. The staphylococcal species was determined using MALDI-TOF MS. The isolates were subjected to mecA-PCR, macrorestriction analysis, and antimicrobial susceptibility testing. MRSA were present in five nasal swabs of the 55 employees tested and in six environmental samples, MRSP in two employees (nasal and hand swabs, each) and in three environmental samples. All isolates harboured mecA. Susceptibility testing revealed that all but one of the isolates were multiresistant. All isolates were resistant to β-lactams and fluoroquinolones. All but one of the isolates were resistant to macrolides and lincosamides. A single MRSA was resistant to gentamicin. All MRSP were resistant to trimethoprim/sulfamethoxazole and non-susceptible to gentamicin. One isolate was also resistant to tetracycline. Macrorestriction analysis revealed three main SmaI patterns for MRSA and two main SmaI patterns for MRSP. All environmental isolates were found in areas of high people and animal traffic, such as dog ward areas, waiting and triage rooms. The finding of indistinguishable MRSA or MRSP among employees and in the environment of the small animal hospital suggests the possibility of transfer of these bacteria between humans, animals, and the hospital environment.

PMID: 29981702 [PubMed - in process]

https://ift.tt/2Ljylqm

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

IgG4-Related Disease of the Thyroid Gland Requiring Emergent Total Thyroidectomy: A Case Report.

Head Neck Pathol. 2018 May 31;:

Authors: Zhao Z, Lee YJ, Zheng S, Khor LY, Lim KH

Abstract
IgG4-related disease of the thyroid gland is a recently recognized subtype of thyroiditis, often with rapid progression requiring surgical treatment. It is considered as a spectrum of disease varying from early IgG4-related Hashimoto's thyroiditis (HT) pattern to late fibrosing HT or Riedel's thyroiditis patterns. Here, we report a 47-year-old Malay woman presenting with progressively painless neck swelling over 3 years and subclinical hypothyroidism. Computed tomography (CT) scan revealed diffuse thyroid enlargement (up to 13 cm) with retrosternal extension and without regional lymphadenopathy. Fine needle aspiration of the thyroid showed a limited number of follicular epithelial cell groups with widespread Hurthle cell change and scanty background colloid, but no evidence of lymphocytosis. The cytologic features fell into the category of 'atypia of undetermined significance'. Subsequently, the patient developed hypercapnic respiratory failure secondary to extrinsic upper airway compression by the thyroid mass and underwent emergent total thyroidectomy. Histology of the thyroid showed diffuse dense lymphoplasmacytic infiltrate and fibrosis. Follicular cells exhibited reactive nuclear features and some Hurthle cell change. IgG4+ plasma cells were over 40/high power field while overall IgG4/IgG ratio was above 50%. The overall features suggest the diagnosis of IgG4-related disease of the thyroid gland in the form of IgG4-related HT. Post-surgery, the patient was found to have markedly elevated serum IgG4 concentration but PET/CT did not show significant increased fludeoxyglucose uptake in other areas. Her recovery was complicated by a ventilator-associated pneumonia with empyema, limiting early use of corticosteroids for treatment of IgG4-related disease.

PMID: 29855801 [PubMed - as supplied by publisher]

https://ift.tt/2LdmmKu

Immunohistochemical Biomarkers in Diagnosis of Hematolymphoid Neoplasms of Endocrine Organs.

Immunohistochemical Biomarkers in Diagnosis of Hematolymphoid Neoplasms of Endocrine Organs.

Endocr Pathol. 2018 Jun;29(2):176-188

Authors: Kuzu I, Dogan A

Abstract
The hematolymphoid infiltrations are challenging lesions in endocrine organs and tissues. The fourth edition of WHO classification of tumors of endocrine organs and the fourth edition of WHO classification of tumors of hematopoietic and lymphoid tissues are recently published. The updates in both fields include some new disease descriptions and prognostic markers. Our aim in this review article is to give practical diagnostic information about the most frequently seen hematolymphoid involvements of the pituitary gland, thyroid, and adrenal tissue. We designed the text in the order of organs and the contents according to the disease frequency. The pituitary gland and cellar region are the most frequently involved with Langerhans cell histiocytosis. Although it is very rare, Erdheim-Chester disease has recently been included in the classification and still needs more clear diagnostic definitions. Lymphoproliferative thyroid lesions and presentations create diagnostic problems for the pathologists. IGG4-related disease and its relation with thyroiditis is a new concept. There are many unknowns on pathobiology of the disease spectrum and discussion on defined diagnostic criteria of the IGG4-related thyroid diseases. The overlapping features of thyroiditis and primary thyroid lymphomas also create diagnostic difficulties. The frequently recognized primary hematolymphoid lesions of the endocrine organs may not be difficult to diagnose since they are expected lesions. The secondary involvement of hematolymphoid neoplasia may be more difficult to diagnose for an endocrine pathologist. In this review article, we aim to give brief description of the diseases and practical diagnostic approach by using optimum markers guided by the latest WHO classifications.

PMID: 29855797 [PubMed - in process]

https://ift.tt/2LUxL2T

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Coronary Toxicities of Anti-PD-1 and Anti-PD-L1 Immunotherapies: a Case Report and Review of the Literature and International Registries

Abstract

Immunotherapy medications that target programmed death 1 protein (PD-1) and programmed death-ligand 1 (PD-L1), such as nivolumab, pembrolizumab, and atezolizumab, are currently used in the first- or second-line treatment of non-small cell lung cancers, among other indications. However, these agents are associated with immune-related side effects, the most common of which are endocrinopathies, colitis, hepatitis, and interstitial pneumonitis. In contrast, coronary toxicities are rarely reported and remain poorly understood. Here, we describe the case of a patient who developed an acute coronary syndrome when treated with nivolumab as second-line therapy for metastatic pulmonary adenocarcinoma. A review of the literature, the French pharmacovigilance registry, and the World Health Organization pharmacovigilance database led to the identification of four cases of patients with coronary manifestations attributable to anti-PD1 immunotherapy (with no reported cases of patients undergoing anti-PD-L1 immunotherapy), which we describe herein. The potential mechanisms causing adverse coronary reactions to this type of therapy, which is used to treat lung cancer as well as other solid and hematological neoplastic diseases, are also discussed.

https://ift.tt/2Lg41Nl

MicroRNAs as Mediators of Resistance Mechanisms to Small-Molecule Tyrosine Kinase Inhibitors in Solid Tumours

Abstract

Receptor tyrosine kinases (RTKs) are widely expressed transmembrane proteins that act as receptors for growth factors and other extracellular signalling molecules. Upon ligand binding, RTKs activate intracellular signalling cascades, and as such are involved in a broad variety of cellular functions including differentiation, proliferation, migration, invasion, angiogenesis, and survival under physiological as well as pathological conditions. Aberrant RTK activation can lead to benign proliferative conditions as well as to various forms of cancer. Indeed, more than 70% of the known oncogene and proto-oncogene transcripts involved in cancer code for RTKs. Consequently, these receptors are broadly studied as targets in the treatment of different tumours, and a large variety of small-molecule tyrosine kinase inhibitors (TKIs) are approved for therapy. In most cases, patients develop resistance to the TKIs within a short time. MicroRNAs are short (18–22 nucleotides) non-protein-coding RNAs that fine-tune cell homeostasis by controlling gene expression at the post-transcriptional level. Deregulation of microRNAs is common in many cancers, and increasing evidence exists for an important role of microRNAs in the development of resistance to therapies, including TKIs. In this review we focus on the role of microRNAs in mediating resistance to small-molecule TKIs in solid tumours.

https://ift.tt/2NMPN84

Preparation of Folic Acid-Targeted Temperature-Sensitive Magnetoliposomes and their Antitumor Effects In Vitro and In Vivo

Abstract

Background

Ovarian cancer is a common gynecologic malignancy with poor prognosis, requiring innovative new therapeutic strategies. Temperature-controlled drug delivery to cancer cells represents a novel, promising, targeted treatment approach.

Objective

We prepared folate receptor-targeted thermosensitive liposomes wrapped with the HSP90 inhibitor 17-AAG and superparamagnetic material (17-AAG/MTSLs-FA), and tested the efficacy of these targeted magnetoliposomes in vitro and in vivo.

Methods

Magnetic thermosensitive liposomes wrapped with 17-AAG were coprecipitated with Fe₃O₄ magnetic nanoparticles and prepared by a rotary evaporation method. Experiments were conducted with SKOV3 human ovarian cancer cells and MCF7 human breast carcinoma cells to evaluate the anti-tumor effects.

Results

17-AAG/MTSLs-FA prepared in this study met the basic requirements for therapeutic application. The preparation method is relatively simple and the raw materials are readily available. The product exhibited strong magnetism, high encapsulation efficiencies, and satisfactory performance. The liposomes combined with hyperthermia significantly inhibited the proliferation of SKOV3 cells and induced apoptosis. Experiments using a mouse subcutaneous model as well as an ascites tumor xenograft model indicated that 17-AAG/MTSLs-FA was stable in vivo and effectively targeted tumor tissues expressing the folate receptor.

Conclusions

Folic acid-conjugated 17-AAG magnetic thermosensitive liposomes in combination with an alternating magnetic field for heating can achieve a synergistic anti-tumor effect of chemotherapy and heat treatment, potentially offering a new method for ovarian cancer treatment.

https://ift.tt/2ufSbLM

Targeted Next-Generation Sequencing in Men with Metastatic Prostate Cancer: a Pilot Study

Abstract

Introduction

Tumor profiling by targeted next-generation sequencing (tNGS) and personalized treatment based on these results is becoming increasingly common in patients with metastatic solid tumors, but it remains unclear whether this strategy results in benefit to patients with metastatic prostate cancer (mPCa).

Objective

To assess the clinical utility of tNGS in treatment decision-making for patients with mPCa.

Patients and Methods

Patients with available genomic profiling using tumor tissue (FoundationOne, F1) or cell-free DNA (FoundationACT, Guardant360) were included. Targetable genomic alterations (tGA) included a change in the copy number or mutations in DNA repair genes, mismatch repair genes, PTEN, cyclin-dependent kinases, ERBB2, BRAF, TSC, and the PIK3/mTOR pathway.

Results

The study included 66 patients, 86% of which had metastatic castration-resistant prostate cancer (mCRPC), and who had received a median of 3 (range 0–7) treatments prior to tNGS. The most frequent alterations were found in TP53 (42%), PTEN (35%), androgen receptor (AR) (30%), DNA repair (30%), PIK3CA signaling pathway (21%), cyclin-dependent kinases (15%), BRAF (9%), and MMR/MSI (6%) genes. Among the 45 (68%) tGA+ patients, tNGS influenced treatment in 13 (29%) [PARP inhibitor (n = 7), mTOR inhibitor (n = 4), anti-PD-1 (n = 2), anti-HER2 (n = 1)]. The median progression-free survival (PFS) was 4.1 months [95% confidence interval (CI), 2.8–5.4]. Among tGA+ patients who did not receive tNGS-based therapy, systemic treatment (n = 17) included chemotherapy (71%), new generation anti-androgen therapy (24%), and cabozantinib (6%); the median PFS was 4.3 months (95% CI, 2.6–6.0; p = 0.7 for tGA+ with personalized therapy vs. tGA+ without personalized therapy).

Conclusion

In this cohort, the use of tNGS was feasible, detected frequent genomic alterations, and was used late in the disease course. Further studies and larger portfolios of targeted therapy trials are needed to maximize the benefit of tNGS in this population.

https://ift.tt/2Lfeusb

Growing Role of Regorafenib in the Treatment of Patients with Sarcoma

Abstract

Sarcomas encompass a group of rare solid tumors responsible for approximately 1% of all cancer-related deaths in the United States each year. Subtypes include, but are not limited to, soft tissue sarcomas (STS) such as leiomyosarcoma, liposarcoma, pleomorphic sarcoma, and gastrointestinal stromal tumor (GIST). Treatment options for patients with STS vary depending on, among other factors, histological subtype. Data from a mix of phase 2 and phase 3 trials have suggested that the orally available multikinase inhibitor regorafenib may have efficacy in patients with STS who have progressed on previous lines of systemic therapy. Some clinical benefit of regorafenib has been shown in patients with leiomyosarcoma, synovial sarcoma, GIST, Ewing's sarcoma, and other sarcoma subtypes, suggesting a broad spectrum of potential activity in this population. Studies have also shown that the safety profile of regorafenib is acceptable in these patients, with adverse events that can be managed through dose reductions and/or interruptions as well as other supportive measures.

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BIM Deletion Polymorphism Confers Resistance to Osimertinib in EGFR T790M Lung Cancer: a Case Report and Literature Review

Abstract

The third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) osimertinib (AZD9291) has shown significant clinical efficacy against the EGFR T790M mutation in non-small cell lung cancer (NSCLC) patients. However, resistance inevitably occurs, and the mechanisms leading to treatment failure need to be further investigated. The B-cell lymphoma 2 (BCL-2)-like 11 (BIM) deletion polymorphism, which occurs at a frequency of 21% in East Asians but is absent in African and European populations, has been associated with resistance to first-generation EGFR TKIs, such as gefitinib and erlotinib; and is a poor prognostic factor for NSCLC patients with EGFR mutations. Nevertheless, the significance of this BIM deletion polymorphism in the resistance to osimertinib has not been reported. Here, we show for the first time that a NSCLC patient harboring the EGFR L858R/T790M mutations, as well as the BIM deletion polymorphism, exhibited poor clinical outcomes with osimertinib treatment. This result suggests that the BIM deletion polymorphism might have prognostic value for determining NSCLC patient outcomes following osimertinib treatment.

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MiR-146b protect against sepsis induced mice myocardial injury through inhibition of Notch1

Abstract

Myocardial dysfunction is a major cause of death in sepsis. MicroRNA-146b (miR-146b) has been reported to be related to myocardial disease. However, the role of miR-146b in sepsis as well as myocardial injury is still unclear. Septic cardiac dysfunction in mice was induced by cecal ligation and puncture (CLP) and miR-146b was found increased significantly in the myocardium tissue of CLP mice. It was found that up-regulation of miR-146b by agomiR injection suppressed expression of IL-1β in mice as well as myocardium apoptosis in CLP mice. However, suppression of miR-146b by antagomiR injection had inverse effects. Notch1 was identified as a target gene of miR-146b by bioinformatics analysis. And it was verified that in cardiomyocytes, the decrease of miR146b led to increase of both the mRNA and protein level of Notch1 and vice versa. In septic mice serum stimulated cardiomyocytes, up-regulation of miR-146b decreased the level of Notch1 and Hes1. The knockout of Notch1 in transgenic mice showed that the deficiency of Notch1 improved myocardial injury induced by CLP operation. The apoptosis of cardiomyocytes was relieved and the expression of IL-1β was decreased. In conclusion, miR-146b targets to Notch1 and protected cardiomyocytes against inflammation and apoptosis.

https://ift.tt/2NNeph4

Cellular and subcellular localization of uncoupling protein 2 in the human kidney

Abstract

The uncoupling protein-2 (UCP2) is an anion transporter that plays a key role in the control of intracellular oxidative stress. In animal models UCP2 downregulation has several pathological sequelae, particularly affecting the vasculature and the kidney. Specifically, in these models kidney damage is highly favored in the absence of UCP2 in the context of experimental hypertension. Confirmations of these data in humans awaits further information, as no data are yet available concerning the cell-type and subcellular expression in the human kidney. In the present study, we aimed to characterize the UCP2 protein distribution in human kidney biopsies. In humans UCP2 is mainly localized in proximal convoluted tubule cells, with an intracytoplasmic punctate staining. UCP2 positive puncta are often localized at the interface between the endoplasmic reticulum and the mitochondria. Glomerular structures do not express UCP2 at detectable levels. The expression of UCP2 in proximal tubular cells may explain their relative propensity to damage in pathological conditions including the hypertensive disease.

https://ift.tt/2Jof2dF

Human urine-derived stem cells play a novel role in the treatment of STZ-induced diabetic mice

Abstract

Human urine-derived stem cells (hUSCs) are a potential stem cell source for cell therapy. However, the effect of hUSCs on glucose metabolism regulation in type 1 diabetes was not clear. Therefore, the aim of the study was to evaluate whether hUSCs have protective effect on streptozotocin (STZ)-induced diabetes. hUSCs were extracted and cultivated with a special culture medium. Flow cytometry analysis was applied to detect cell surface markers. BALB/c male nude mice were either injected with high-dose STZ (HD-STZ) or multiple low-dose STZ (MLD-STZ). Serum and pancreatic insulin were measured, islet morphology and its vascularization were investigated. hUSCs highly expressed CD29, CD73, CD90 and CD146, and could differentiate into, at least, bone and fat in vitro. Transplantation of hUSCs into HD-STZ treated mice prolonged the median survival time and improved their blood glucose, and into those with MLD-STZ improved the glucose tolerance, islet morphology and increased the serum and pancreas insulin content. Furthermore, CD31 expression increased significantly in islets of BALB/c nude mice treated with hUSCs compared to those of un-transplanted MLD-STZ mice. hUSCs could improve the median survival time and glucose homeostasis in STZ-treated mice through promoting islet vascular regeneration and pancreatic beta-cell survival.

https://ift.tt/2EZM2qm

Three-dimensional reconstructed eccrine sweat glands with vascularization and cholinergic and adrenergic innervation

Abstract

Functional integrity of the regenerated tissues requires not only structural integrity but also vascularization and innervation. We previously demonstrated that the three-dimensional (3D) reconstructed eccrine sweat glands had similar structures as those of the native ones did, but whether the 3D reconstructed glands possessing vascularization and innervation was still unknown. In the study, Matrigel-embedded eccrine sweat gland cells were implanted under the inguinal skin. Ten weeks post-implantation, the vascularization, and innervation in the 10-week reconstructed eccrine sweat glands and native human eccrine sweat glands were detected by immunofluorescence staining. The results showed that the fluorescent signals of general neuronal marker protein gene product 9.5, adrenergic nerve fiber marker tyrosine hydroxylase, and cholinergic nerve fiber markers acetylcholinesterase and vasoactive intestinal peptide embraced the 3D reconstructed glands in circular patterns, as the signals appeared in native eccrine sweat glands. There were many CD31- and von Willebrand factor-positive vessels growing into the plugs. We demonstrated that the 3D reconstructed eccrine sweat glands were nourished by blood vessels, and we for the first time demonstrated that the engineering sweat glands were innervated by both cholinergic and adrenergic fibers. In conclusion, the 3D reconstructed eccrine sweat glands may have functions as the native ones do.

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Correction to: BrdU/EdU dual labeling to determine the cell-cycle dynamics of defined cellular subpopulations

In the original publication of the article, two errors were made in describing the equations for T_c.

https://ift.tt/2NQjaGE

Cell type specific expression of Follistatin-like 1 (Fstl1) in mouse embryonic lung development

Abstract

Follistatin like-1 (Fstl1) is a secreted glycoprotein and can be up-regulated by TGF-β1. To better study the function of Fstl1 in lung development, we examined Fstl1 expression in the developing lung, in a cell type specific manner, using a tamoxifen inducible Fstl1-reporter mouse strain. Our results show that Fstl1 is ubiquitously expressed at saccular stage in the developing lung. At E18.5, Fstl1 expression is robust in most type of mesenchymal cells, including airway smooth muscle cells surrounding airways, vascular smooth muscle cells, endothelial cells, and vascular pericytes from blood vessel, but not PDGFRα⁺ fibroblasts in the distal alveolar sacs. Meanwhile, relative weak and sporadic signals of Fstl1 expression are observed in epithelium, including a subgroup of club cells in proximal airways and a few type II alveolar epithelial cells in distal airways. Our data help to understand the critical role of Fstl1 in lung development and lung disease pathogenesis.

https://ift.tt/2LkLteW

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Σάββατο 14 Ιουλίου 2018

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