Bacterial Outer Membrane Vesicles Promote Lung Inflammatory Responses and Macrophage Activation via Multi-Signaling Pathways.

Emerging evidence suggests that Gram-negative bacteria release bacterial outer membrane vesicles (OMVs) and that these play an important role in the pathogenesis of bacterial infection-mediated inflammatory responses and organ damage. Despite the fact that scattered reports have shown that OMVs released from Gram-negative bacteria may function via the TLR2/4-signaling pathway or induce pyroptosis in macrophages, our study reveals a more complex role of OMVs in the development of inflammatory lung responses and macrophage pro-inflammatory activation. We first confirmed that various types of Gram-negative bacteria release similar OMVs which prompt pro-inflammatory activation in both bone marrow-derived macrophages and lung alveolar macrophages.

Pretreated household materials carry similar filtration protection against pathogens when compared with surgical masks.

Objective: The past 4 months, the emergence and spread of novel 2019 SARS-Cov-2 (COVID-19) has led to a global pandemic which is rapidly depleting supplies of personal protective equipment worldwide. There are currently over 1.6 million confirmed cases of COVID-19 worldwide which has resulted in more the 100,000 deaths.

APE1 Promotes Pancreatic Cancer Proliferation through GFRα1/Src/ERK Axis-Cascade Signaling in Response to GDNF.

Pancreatic cancer is the worst exocrine gastrointestinal cancer leading to the highest mortality. Recent studies reported that aberrant expression of apurinic/apyrimidinic endodeoxyribonuclease 1 (APE1) is involved in uncontrolled cell growth. However, the molecular mechanism of APE1 biological role remains unrevealed in pancreatic cancer progression.

Scavenger Receptor Class A to E Involved in Various Cancers.

Scavenger receptors typically bind to multiple ligands on a cell surface, including endogenous and modified host-derived molecules and microbial pathogens. They promote the elimination of degraded or harmful substances such as non-self or altered-self targets through endocytosis, phagocytosis, and adhesion. Currently, scavenger receptors are subdivided into eight classes based on several variations in their sequences due to alternative splicing.

Therapeutic Effects of Synthetic Antimicrobial Peptides, TRAIL and NRP1 Blocking Peptides in Psoriatic Keratinocytes.

Psoriasis is a chronic, recurrent, heterogeneous, cutaneous inflammatory skin disease for which there is no cure. It affects approximately 7.5 million people in the United States.

Melanoma Cell Death Mechanisms.

Over recent years, several new molecular and immunogenic therapeutic approaches to melanoma treatment have been approved and implemented in clinical practice. Mechanisms of resistance to these new therapies have become a major problem. Mutation-specific pharmacotherapy can result in simultaneous emergence of resistant clones at many separate body sites despite an initially positive therapeutic response.

The regulation of combined treatment-induced cell death with recombinant TRAIL and bortezomib through TRAIL signaling in TRAIL-resistant cells.

Background: Multiple trials have attempted to demonstrate the effective induction of cell death in TRAIL-resistant cancer cells, including using a combined treatment of recombinant TRAIL and various proteasome inhibitors. These studies have yielded limited success, as the mechanism of cell death is currently unidentified. Understanding this mechanism's driving forces may facilitate the induction of cell death in TRAIL-resistant cancer cells.

Therapeutic Inhibitors against Mutated BRAF and MEK for the Treatment of Metastatic Melanoma.

Melanoma is one of the most aggressive cancers in the world and is responsible for the majority of skin cancer deaths. Recent advances in the field of immunotherapy using active, adoptive, and antigen-specific therapeutic approaches, have generated the expectation that these technologies have the potential to improve the treatment of advanced malignancies, including melanoma. Treatment options for metastatic melanoma patients have been dramatically improved by the FDA approval of new therapeutic agents including vemurafenib, dabrafenib, and sorafenib.

The Alpha-Melanocyte-Stimulating Hormone Suppresses TLR2-Mediated Functional Responses through IRAK-M in Normal Human Keratinocytes.

Alpha-melanocyte stimulating hormone (α-MSH) is a highly conserved 13-aa neuropeptide derived from pro-opiomelanocortin by post-translational processing, which has been reported to exhibit potent anti-inflammatory activity and a wide range of immunosuppressive activities in the skin. However, the regulatory effect of α-MSH is not completely clear in cutaneous innate immunity. In this study, we investigate the functional regulation of α-MSH in TLR2-mediated inflammatory responses in normal human keratinocytes (HKs).

Suppression of Propionibacterium acnes Infection and the Associated Inflammatory Response by the Antimicrobial Peptide P5 in Mice.

The cutaneous inflammation associated with acne vulgaris is caused by the anaerobic bacterium Propionibacterium acnes through activation of the innate immune system in the skin. Current standard treatments for acne have limitations that include adverse effects and poor efficacy in many patients, making development of a more effective therapy highly desirable. In the present study, we demonstrate the protective effects of a novel customized α-helical cationic peptide, P5, against P.

Mycophenolate antagonizes IFN-γ-induced catagen-like changes via β-catenin activation in human dermal papilla cells and hair follicles.

Recently, various immunosuppressant drugs have been shown to induce hair growth in normal hair as well as in alopecia areata and androgenic alopecia; however, the responsible mechanism has not yet been fully elucidated. In this study, we investigate the influence of mycophenolate (MPA), an immunosuppressant, on the proliferation of human dermal papilla cells (hDPCs) and on the growth of human hair follicles following catagen induction with interferon (IFN)-γ. IFN-γ was found to reduce β-catenin, an activator of hair follicle growth, and activate glycogen synthase kinase (GSK)-3β, and enhance expression of the Wnt inhibitor DKK-1 and catagen inducer transforming growth factor (TGF)-β2.

Colonization and infection of the skin by S. aureus: immune system evasion and the response to cationic antimicrobial peptides.

Staphylococcus aureus (S. aureus) is a widespread cutaneous pathogen responsible for the great majority of bacterial skin infections in humans. The incidence of skin infections by S.

Antimicrobial and anti-inflammatory effects of Cecropin A(1-8)-Magainin2(1-12) hybrid peptide analog p5 against Malassezia furfur infection in human keratinocytes.

The lipophilic fungus Malassezia furfur (M. furfur) is a commensal microbe associated with several chronic diseases such as pityriasis versicolor, folliculitis, and seborrheic dermatitis. Because M.

Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition.

Background: Curcumin, a natural polyphenolic compound, has been shown to reduce cardiomyocyte growth. Angiotensin II type 1 receptor (AT1R) and lectin-like oxidized low density lipoprotein (ox-LDL) receptor-1 (LOX-1) are major stimuli for cardiomyocyte growth via activation of oxidant signals. We postulated that curcumin may reduce Ang II-mediated cardiomyocyte growth via AT1R and LOX-1 inhibition.

Genomics of cardiac remodeling in angiotensin II-treated wild-type and LOX-1-deficient mice.

We studied the gene expression profile during cardiac hypertrophy induced by angiotensin (ANG) II in wild-type mice and the influence of LOX-1 deletion on the gene expression profile. Wild-type and LOX-1 knockout mice were given saline or ANG II infusion for 4 wk. The saline-treated LOX-1 knockout mice showed upregulation of several genes including Ddx3y and Eif2s3y.

Curcumin reduces angiotensin II-mediated cardiomyocyte growth via LOX-1 inhibition.

Background: Curcumin, a natural polyphenolic compound, has been shown to reduce cardiomyocyte growth. Angiotensin II type 1 receptor (AT1R) and lectin-like oxidized low density lipoprotein (ox-LDL) receptor-1 (LOX-1) are major stimuli for cardiomyocyte growth via activation of oxidant signals. We postulated that curcumin may reduce Ang II-mediated cardiomyocyte growth via AT1R and LOX-1 inhibition.

Modulation of flower colour by rationally designed dominant-negative chalcone synthase.

The intensity of flower colour, mainly determined by the amount of anthocyanin, is an important horticultural trait. To modulate flower colour intensity, post-transcriptional gene silencing (PTGS)-based technology has been widely used. The constraint of PTGS, however, is that it requires a high degree of conservation in the nucleotide sequences of the target and the silencer.

Claudin-7 is highly expressed in chromophobe renal cell carcinoma and renal oncocytoma.

Claudin-7 has recently been suggested to be a distal nephron marker. We tested the possibility that expression of claudin-7 could be used as a marker of renal tumors originating from the distal nephron. We examined the immunohistochemical expression of claudin-7 and parvalbumin in 239 renal tumors, including 179 clear cell renal cell carcinoma (RCC)s, 29 papillary RCCs, 20 chromophobe RCCs, and 11 renal oncocytomas.