TLR2 and TLR9 Blockade Using Specific Intrabodies Inhibits Inflammation-Mediated Pancreatic Cancer Cell Growth.

Pancreatic cancer (pancreatic ductal adenocarcinoma, PDAC) remains a deadly cancer worldwide with a need for new therapeutic approaches. A dysregulation in the equilibrium between pro- and anti-inflammatory responses with a predominant immunosuppressive inflammatory reaction in advanced stage tumors seem to contribute to tumor growth and metastasis. The current therapies do not include strategies against pro-tumorigenic inflammation in cancer patients.

Platelet-derived growth factor (PDGF) cross-signaling via non-corresponding receptors indicates bypassed signaling in colorectal cancer.

Platelet-derived growth factor (PDGF) signaling, besides other growth factor-mediated signaling pathways like vascular endothelial growth factor (VEGF) and epidermal growth factor (EGF), seems to play a crucial role in tumor development and progression. We have recently provided evidence for upregulation of PDGF expression in UICC stage I-IV primary colorectal cancer (CRC) and demonstrated PDGF-mediated induction of PI3K/Akt/mTOR signaling in CRC cell lines. The present study sought to follow up on our previous findings and explore the alternative receptor cross-binding potential of PDGF in CRC.

Adenosinergic Pathway and Linked Suppression: Two Critical Suppressive Mechanisms of Human Donor Antigen Specific Regulatory T Cell Lines Expanded Post Transplant.

Regulatory T cells are an important component of an immune response shaping the overall behavior to potential antigens including alloantigens. Multiple mechanisms have been shown to contribute towards developing and sustaining a immunological regulatory response. One of the described contact dependent suppressive mechanisms regulatory cells have been shown to utilize is through the production of adenosine from extracellular ATP mediated by CD39 and CD73.

Deletion of STAT3 from Foxd1 cell population protects mice from kidney fibrosis by inhibiting pericytes trans-differentiation and migration.

Signal transduction and activator of transcription 3 (STAT3) is a key transcription factor implicated in the pathogenesis of kidney fibrosis. Although Stat3 deletion in tubular epithelial cells is known to protect mice from fibrosis, vFoxd1 cells remains unclear. Using Foxd1-mediated Stat3 knockout mice, CRISPR, and inhibitors of STAT3, we investigate its function.

PDE4D targeting enhances anti-tumor effects of sorafenib in clear cell renal cell carcinoma and attenuates MAPK/ERK signaling in a CRAF-dependent manner.

Clear cell renal cell carcinoma (ccRCC) is the most lethal form of kidney cancer and effective treatment regimens are yet to be established. Tyrosine kinase inhibitors (TKI) have widely been used as ccRCC therapeutics, but their efficacy is limited due to accompanying resistance mechanisms. Previous studies have provided substantial evidence for crosstalk between cAMP and the MAPK/ERK signaling pathway.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

Background: CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC).

Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas.

Methods: A total of 156 patients with UICC stage I-IV adenocarcinomas (n=122) and adenomas (n=34) were analyzed.

The Beneficial Role of Auricular Point Pressure in Insomnia and Anxiety in Isolated COVID-19 Patients.

Background: Coronavirus disease 2019 (COVID-19) causes psychological distress and can have a negative impact on the general mental health and rehabilitation in affected patients under currently implemented isolation guidelines. Auricular point pressure (APP) as well-established technique in traditional Chinese medicine may help to relieve sleep disturbance and anxiety in COVID-19 patients.

Methods: During the early phase of the epidemic/pandemic, patients were enrolled in this study (02/2020 until 03/2020 = 84).

IS THERE A CLINICAL PATHOLOGICAL CORRELATION OF COLORECTAL ADENOCARCINOMA WITH THE IMMUNOHISTOCHEMICAL EXPRESSION OF OPN AND ABCB5?

Background: OPN ABCB5. Studies with biomarkers in TMA (tissue microarray) have been showing important results regarding its expression in colon cancer.

Aim: Correlate the expression profile of the OPN and ABCB5 biomarkers with the epidemiological and clinicopathological characteristics of the patients, the impact on the progression of the disease and the death.

ARE STEM CELL MARKER EXPRESSION AND CD133 ANALYSIS RELEVANT TO DIFFERENTIATE COLORECTAL CANCER?

Background: A) CD133+ cytoplasmic B) AXL+ combined C) c-MYC+ nuclear. CD133 and AXL have been described as cancer stem cell markers, and c-MYC as a key regulatory cellular mechanism in colorectal cancer (CRC).

Aim: Evaluate the prognostic role of the biomarkers CD133, AXL and c-MYC and their association with clinicopathologic characteristics in colorectal adenocarcinomas and adenomas.

Prognostic significance of CD133 and ABCB5 expression in papillary thyroid carcinoma.

Expression of CD133 and ABCB5 is associated with tumor aggressiveness, but evidence in papillary thyroid cancer (PTC) is lacking. We correlated CD133 and ABCB5 expression with pathological characteristics and factors of worse prognosis in PTC. Samples of 119 PTCs and 40 controls (goiters) were distributed in 8 tissue microarray blocks and evaluated with immunohistochemistry using anti-CD133 and anti-ABCB5 antibodies.

Modulation of Calcium Homeostasis May Be Associated with Susceptibility to Renal Cell Carcinoma in Diabetic Nephropathy Rats.

Introduction: Clinical studies have indicated a relationship between diabetic nephropathy (DN) and the incidence and prevalence of renal cell carcinoma (RCC). However, the mechanism linking diabetic nephropathy and renal cell carcinoma has not yet to be identified.

Methods: In this study, a total of 42 male Sprague Dawley (SD) rats were randomly assigned to a DN group (n=35) and a control group (n=7).

Topical therapy with rhubarb navel plasters in patients with chronic constipation: Results from a prospective randomized multicenter study.

Ethnopharmacological Relevance: Constipation is a functional gastrointestinal disorder and one of the most prevalent conditions encountered in primary care settings. Rhubarb navel dressings have been used for more than 2,000 years in Chinese medicine to treat constipation. However, the effect of topical rhubarb administration has still not been well recognized and this strategy is not yet established as an evidence-based approach.

KMP01D Demonstrates Beneficial Anti-inflammatory Effects on Immune Cells: An Preclinical Study of Patients With Colorectal Cancer.

Colorectal cancer (CRC) is frequently associated with dysbiosis of the gut microbiome which, together with a compromised gut barrier, can result in perioperative endotoxin leakage into the circulation. Constant local and systemic inflammatory activity is suggested to facilitate metastases formation. Previous studies have pointed to the capacity of a colostrum preparation to neutralize endotoxins within the gastrointestinal tract which could ameliorate associated inflammatory responses and tumor recurrence in affected patients.

Inflammation-induced tissue damage mimicking GvHD in human skin models as test-platform for immunotherapeutics.

With cellular products being on the front run there is a rising demand for non-animal-based test platforms to predict, study and treat undesired immunity. Here, we generated human organotypic skin models from human biopsies isolating and expanding keratinocytes, fibroblasts and microvascular endothelial cells finally allowing to seed these components on a collagen matrix or a biological vascularized scaffold matrix in a bioreactor. Afterwards, we were able to induce inflammation-based tissue damage by pre-stimulated mismatched allogeneic lymphocytes and/or inflammatory cytokine containing supernatants histomorphologically mimicking severe graft versus host disease (GvHD) of the skin.

Expression of Tumor-mediated CD137 ligand in human colon cancer indicates dual signaling effects.

CD137-targeting immune therapy, which activates anti-tumor T effector cell responses, seems to be an attractive concept in clinical oncology. Recent evidence has demonstrated that tumor cells besides T cells and antigen-presenting cells are able to express CD137 and CD137L. Here we aimed to identify CD137/CD137L expression in established colon cancer cell lines and primary tumors (UICC stages I-IV) from patients with documented long-term follow-up.

The axis of local cardiac endogenous Klotho-TGF-β1-Wnt signaling mediates cardiac fibrosis in human.

Background: Cardiovascular fibrosis is a major contributor to cardiovascular disease, the primary cause of death in patients with chronic kidney disease (CKD). We previously reported expression of endogenous Klotho in human arteries, and that CKD is a state of Klotho deficiency, resulting in vascular calcification, but myocardial expression of Klotho is poorly understood. This study aimed to further clarify endogenous Klotho's functional roles in cardiac fibrosis in patients with underlying CKD.

Perinatal Exposure Is Associated With Increased Risk of Late Onset Sepsis and Imbalanced Inflammation in Preterm Infants and May Add to Lung Injury.

Controversy remains concerning the impact of on preterm neonatal morbidity. Prospective single-center study in very low birth weight infants <30 weeks' gestation. Cord blood and initial nasopharyngeal swabs were screened for and using culture technique and polymerase chain reaction.

Comparative Analysis of Inflammatory Cytokine Release and Alveolar Epithelial Barrier Invasion in a Transwell Bilayer Model of Mucormycosis.

Understanding the mechanisms of early invasion and epithelial defense in opportunistic mold infections is crucial for the evaluation of diagnostic biomarkers and novel treatment strategies. Recent studies revealed unique characteristics of the immunopathology of mucormycoses. We therefore adapted an alveolar Transwell A549/HPAEC bilayer model for the assessment of epithelial barrier integrity and cytokine response to , and .

Tissue microarray technology and collagen evaluation to analyze surgical trauma performed with usual blade or ultrasonic harmonic scalpels in rats.

Purpose: To compare wound healing performed with cold blade (CSB) and ultrasonic harmonic scalpel (UHS) in the abdominal aponeurosis of rats.

Methods: Eighty Wistar rats divided into two groups and underwent midline incision in the linea alba with cold blade and harmonic ultrasonic scalpel. Analysis were performed in subgroups of 10 animals after 3, 7, 14 and 21 days.

Evaluation of Aspergillus and Mucorales specific T-cells and peripheral blood mononuclear cell cytokine signatures as biomarkers of environmental mold exposure.

Mold specific T-cells have been described as a supportive biomarker to monitor invasive mycoses and mold exposure. This study comparatively evaluated frequencies and cytokine profiles of Aspergillus fumigatus and Mucorales reactive T-cells depending on environmental mold exposure. Peripheral blood mononuclear cells (PBMCs) obtained from 35 healthy donors were stimulated with mycelial lysates of A.

ATP-binding cassette member B5 (ABCB5) promotes tumor cell invasiveness in human colorectal cancer.

ABC member B5 (ABCB5) mediates multidrug resistance (MDR) in diverse malignancies and confers clinically relevant 5-fluorouracil resistance to CD133-expressing cancer stem cells in human colorectal cancer (CRC). Because of its recently identified roles in normal stem cell maintenance, we hypothesized that ABCB5 might also serve MDR-independent functions in CRC. Here, in a prospective clinical study of 142 CRC patients, we found that ABCB5 mRNA transcripts previously reported not to be significantly expressed in healthy peripheral blood mononuclear cells are significantly enriched in patient peripheral blood specimens compared with non-CRC controls and correlate with CRC disease progression.

Ureaplasma isolates stimulate pro-inflammatory CC chemokines and matrix metalloproteinase-9 in neonatal and adult monocytes.

Being generally regarded as commensal bacteria, the pro-inflammatory capacity of Ureaplasma species has long been debated. Recently, we confirmed Ureaplasma-driven pro-inflammatory cytokine responses and a disturbance of cytokine equilibrium in primary human monocytes in vitro. The present study addressed the expression of CC chemokines and matrix metalloproteinase-9 (MMP-9) in purified term neonatal and adult monocytes stimulated with serovar 8 of Ureaplasma urealyticum (Uu) and serovar 3 of U.