The frequency of peripheral PD-1+ TCD4+ cells is reversely associated with serum creatinine levels in recipients of kidney allografts.

The long-term survival of solid organ allografts remains a challenge for organ transplantation systems worldwide. T-cell exhaustion has been supposed to be associated with immunologic tolerance in transplantation and might reflect the immunologic status in recipients. The aim of the present study was to compare the TCD4+ cells of kidney transplant recipients with high and low serum creatinine levels for their expressions of PD-1 and TIGIT as two well-known exhaustion markers. Blood samples were taken from 20 kidney allograft recipients with serum creatinine levels above 2 mg/dL and 20 recipients with creatinine levels below 2 mg/dL. The percentages of PD-1+ CD4+ and TIGIT+ CD4+ cells were analyzed along with the evaluation of TNF-α, IFN-γ, and IL-10 release from peripheral blood mononuclear cells (PBMCs). The patients with serum creatinine levels below 2 mg/dL demonstrated a higher frequency of PD-1+ CD4+ T-cells (p = 0.003) along with lower TNF-α secretion from PBMCs (p = 0.028). The frequency of PD-1 + CD4+ T-cells was reversely correlated with the serum creatinine levels in recipients of kidney allografts (r = 0.59, p < 0.001). Besides, the MFI of TIGIT on TCD4+ cells demonstrated a trend for higher expression in patients with serum creatinine levels below 2 mg/dL (p = 0.070). The expression of PD-1+ on CD4+ T-cells demonstrated a potential for estimation of the immunologic status of the host in interaction with alloantigens. The exhaustion markers could be regarded as potential diagnostic indicators for the evaluation of immunologic tolerance in renal transplantation.

Effect of Curcumin on the Head and Neck Squamous Cell Carcinoma Cell Line HN5.

BACKGROUND: Curcumin has been isolated from the rhizomes of Curcuma longa. Over the years, it has shown outstanding therapeutic potential in various human disorders, including cancers. OBJECTIVE: The aim is to study curcumin's effects on the apoptosis signaling pathway in the head and neck squamous cell carcinoma (HNSCC) cell line HN5. METHODS: The cytotoxicity of curcumin on HN5 cells were assessed. In addition, HN5 cells were also treated with curcumin to evaluate its effect on the caspase-8, -9, Bcl-2, Bax, and Stat3 gene expressions. RESULTS: The results exhibited that cell viability reduced following curcumin treatment in a concentration- dependent manner. Curcumin treatment caused decreased expression of Bcl2, with simultaneous upregulation of the Bax/Bcl2 ratio. Curcumin increased caspase-9 expression, did not affect caspase-8, and decreased Stat3 expression. The induction of the mitochondria-dependent apoptosis pathway of curcumin happened by modulating the expression of Bcl2 and Bax genes, resulting in the caspase-9 activation. Furthermore, curcumin decreased the expression of the Stat3 in HN-5 cells. CONCLUSIONS: In conclusion, curcumin showed marked anticancer effects in the HN-5 cell line by modulating Stat-3; Bax/Bcl-2 expression in vitro.

Panels of mRNAs and miRNAs for decoding molecular mechanisms of Renal Cell Carcinoma (RCC) subtypes utilizing Artificial Intelligence approaches.

Renal Cell Carcinoma (RCC) encompasses three histological subtypes, including clear cell RCC (KIRC), papillary RCC (KIRP), and chromophobe RCC (KICH) each of which has different clinical courses, genetic/epigenetic drivers, and therapeutic responses. This study aimed to identify the significant mRNAs and microRNA panels involved in the pathogenesis of RCC subtypes. The mRNA and microRNA transcripts profile were obtained from The Cancer Genome Atlas (TCGA), which were included 611 ccRCC patients, 321 pRCC patients, and 89 chRCC patients for mRNA data and 616 patients in the ccRCC subtype, 326 patients in the pRCC subtype, and 91 patients in the chRCC for miRNA data, respectively. To identify mRNAs and miRNAs, feature selection based on filter and graph algorithms was applied. Then, a deep model was used to classify the subtypes of the RCC. Finally, an association rule mining algorithm was used to disclose features with significant roles to trigger molecular mechanisms to cause RCC subtypes. Panels of 77 mRNAs and 73 miRNAs could discriminate the KIRC, KIRP, and KICH subtypes from each other with 92% (F1-score ≥ 0.9, AUC ≥ 0.89) and 95% accuracy (F1-score ≥ 0.93, AUC ≥ 0.95), respectively. The Association Rule Mining analysis could identify miR-28 (repeat count = 2642) and CSN7A (repeat count = 5794) along with the miR-125a (repeat count = 2591) and NMD3 (repeat count = 2306) with the highest repeat counts, in the KIRC and KIRP rules, respectively. This study found new panels of mRNAs and miRNAs to distinguish among RCC subtypes, which were able to provide new insights into the underlying responsible mechanisms for the initiation and progression of KIRC and KIRP. The proposed mRNA and miRNA panels have a high potential to be as biomarkers of RCC subtypes and should be examined in future clinical studies.

New insights on the monitoring of solid-organ allografts based on immune cell signatures.

Attaining a fair long-term allograft survival remains a challenge for allogeneic transplantation worldwide. Although the emergence of immunosuppressants has caused noticeable progress in the management of immunologic rejection, proper application of these therapeutics and dose adjustments require delicate and real-time monitoring of recipients. Nevertheless, the majority of conventional allograft monitoring approaches are based on organ damage or functional tests that render them unable to predict the rejection events in early time points before the establishment of a functional alloimmune response. On the other hand, biopsy-based methods include invasive practices and are accompanied by serious complications. In recent years, there have been a myriad of attempts on the discovery of reliable and non-invasive approaches for the monitoring of allografts that regarding a close relationship between allografts and hosts' immune system, most of the attempts have been devoted to the studies on the immune response-associated biomarkers. The discovery of gene and protein expression patterns in immune cells along with their phenotypic characterization and secretome analysis as well as tracking the immune responses in allograft tissues and clinical specimens are among the notable attempts taken to discover the non-invasive predictive markers with a proper coincidence to the pathologic condition. Collectively, these studies suggest a list of candidate biomarkers with ideal potentials for early and non-invasive prediction of allograft rejection and shed light on the way towards developing more standardized and reproducible approaches for monitoring the allograft rejection.

Application of Collagen and Mesenchymal Stem Cells in Regenerative Dentistry.

Collagen is an important macromolecule of Extracellular Matrix (ECM) in bones, teeth, and temporomandibular joints. Mesenchymal Stem Cells (MSCs) interact with the components of the ECM such as collagen, proteoglycans, Glycosaminoglycans (GAGs), and several proteins on behalf of variable matrix elasticity and bioactive cues. Synthetic collagen-based biomaterials could be effective scaffolds for regenerative dentistry applications due to mimicking of host tissues' ECM. These biomaterials are biocompatible, biodegradable, readily available, and non-toxic to cells whose capability promotes cellular response and wound healing in the craniofacial region. Collagen could incorporate other biomolecules to induce mineralization in calcified tissues like bone and tooth. Moreover, the addition of these molecules or other polymers to collagen-based biomaterials could enhance mechanical properties, which is important in load-bearing areas such as the mandible. A literature review was performed via a reliable internet database (mainly PubMed) based on MeSH keywords. This review first describes the properties of collagen as a key protein in the structure of hard tissues. Then, it introduces different types of collagens, the correlation between collagen and MSCs, and the methods used to modify collagen in regenerative dentistry, including recent progression on the regeneration of periodontium, dentin-pulp complex, and temporomandibular joint by applying collagen. The prospects and challenges of collagen-based biomaterials in the craniofacial region are pointd out.

Targeting Mitochondrial Biogenesis with Polyphenol Compounds.

Appropriate mitochondrial physiology is an essential for health and survival. Cells have developed unique mechanisms to adapt to stress circumstances and changes in metabolic demands, by meditating mitochondrial function and number. In this context, sufficient mitochondrial biogenesis is necessary for efficient cell function and haemostasis, which is dependent on the regulation of ATP generation and maintenance of mitochondrial DNA (mtDNA). These procedures play a primary role in the processes of inflammation, aging, cancer, metabolic diseases, and neurodegeneration. Polyphenols have been considered as the main components of plants, fruits, and natural extracts with proven therapeutic effects during the time. These components regulate the intracellular pathways of mitochondrial biogenesis. Therefore, the current review is aimed at representing an updated review which determines the effects of different natural polyphenol compounds from various plant kingdoms on modulating signaling pathways of mitochondrial biogenesis that could be a promising alternative for the treatment of several disorders.

Critical roles of microRNA-196 in normal physiology and non-malignant diseases: Diagnostic and therapeutic implications.

MicroRNAs (miRNAs) have emerged as a critical component of regulatory networks that modulate and fine-tune gene expression in a post-transcriptional manner. The microRNA-196 family is encoded by three loci in the human genome, namely hsa-mir-196a-1, hsa-mir-196a-2, and hsa-mir-196b. Increasing evidence supports the roles of different components of this miRNA family in regulating key cellular processes during differentiation and development, ranging from inflammation and differentiation of stem cells to limb development and remodeling and structure of adipose tissue. This review first discusses about the genomic context and regulation of this miRNA family and then take a bird's eye view on the updated list of its target genes and their biological processes to obtain insights about various functions played by members of the microRNA-196 family. We then describe evidence supporting the involvement of the human microRNA-196 family in regulating critical cellular processes both in physiological and non-malignant inflammatory conditions, highlighting recent seminal findings that carry implications for developing novel therapeutic or diagnostic strategies.

To resist and persist: Important factors in the pathogenesis of Bacteroides fragilis.

Bacteroides fragilis is a most frequent anaerobic pathogen isolated from human infections, particularly found in the abdominal cavity. Different factors contribute to the pathogenesis and persistence of B. fragilis at infection sites. The knowledge of the virulence factors can provide applicable information for finding alternative options for the antibiotic therapy and treatment of B. fragilis caused infections. Herein, a comprehensive review of the important B. fragilis virulence factors was prepared. In addition to B. fragilis toxin (BFT) and its potential role in the diarrhea and cancer development, some other important virulence factors and characteristics of B. fragilis are described including capsular polysaccharides, iron acquisition, resistance to antimicrobial agents, and survival during the prolonged oxidative stress, quorum sensing, and secretion systems.

Expression pattern of miR-21, miR-25 and PTEN in peripheral blood mononuclear cells of patients with significant or insignificant coronary stenosis.

Coronary artery disease (CAD) is primarily caused by atherosclerosis, which is a series of chronic inflammatory processes leading to the initiation and progression of vascular endothelial cell injury enhancing plaque formation. As critical components of the immune system, peripheral blood mononuclear cells (PBMCs) actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in altered PBMC expression pattern. This study explored PBMC expression levels of miR-21, miR-25 and PTEN in patients with angiographically proven significant coronary stenosis (the CAD group), patients with insignificant coronary stenosis (the ICAD group) and healthy subjects, and assessed potentials of PBMC expressions in discriminating groups of study subjects. In-silico analysis was also performed to obtain insights into CAD-related pathways and biological processes that may be influenced by altered miRNA expressions. A reduced level of PBMC miR-21 was observed in the ICAD group compared to the CAD group (P: 0.004) or healthy controls (P: 0.0001). PBMC miR-21 level was negatively correlated with the PTEN expression (Spearman r: -0.43, P: 3.9e-09). The PTEN expression was increased in the CAD or ICAD group compared to the control group (CAD vs. controls P: 0.0003, ICAD vs. controls P: 0.03). A stepwise increase in PBMC miR-25 levels was observed from healthy controls to ICADs and CAD patients (Kruskal-Wallis P: 7.68e-12). PBMC gene expressions had reasonable power to discriminate between pairs of study groups. PBMC miR-21 levels were able to discriminate ICADs from both CADs and controls and miR-25 levels had potentials to differentiate among all pairs of study groups (i.e. CADs-ICADs, CADs-controls, CADs-all other subjects, ICADs-controls). PBMC PTEN expression was able to discriminate patients with CAD or ICAD from control subjects. Overrepresentation enrichment analysis of experimentally validated targets of miR-21 and miR-25 highlighted key biological processes and pathways, such as "angiogenesis" and "leukocyte cell-cell adhesion", that may be influenced by dysregulation of PBMC miR-21 and miR-25. In conclusion, these findings suggest that patients with insignificant coronary stenosis may have a distinct PBMC miRNA expression profile than those with significant stenosis or healthy controls.

Halomonas tabrizica sp. nov., a novel moderately halophilic bacterium isolated from Urmia Lake in Iran.

A novel moderately halophilic, Gram-stain negative and aerobic bacterium, designated strain TBZ21T, was isolated from a water sample of Urmia Lake, Iran. Cells were observed to be non-motile rods with no flagellum, showing positive catalase and oxidase reactions. Strain TBZ21T was found to grow at 10-40 °C (optimum, 30 °C), at pH 7-10 (optimum, pH 8) and in the presence of 1-22% (optimum, 10%). The major fatty acids were identified as C19:0 cyclo ω8c, C16:0, Summed features 3 (C13:0 3-OH and/or iso-C15:1 H) and 8 (C18:1 ω7c and/or C18:1 ω6c) and C12:0 3-OH. The major polar lipids were identified as diphosphatidylglycerol, phosphatidylglycerol, phosphatidylethanolamine and an unidentified phosphoaminolipid. The genomic DNA G+C content of strain TBZ21T was determined to be 63.3 mol%. Phylogenetic analyses based on 16S rRNA gene sequences indicated that strain TBZ21T belongs to the genus Halomonas, and shows high sequence similarities to Halomonas fontilapidosi 5CRT (99.43%), Halomonas ventosae AL12T (98.64%), Halomonas sediminicola CPS11T (98.63%) and Halomonas aestuarii Hb3T (98.08%), and has low similarities (below 98.0%) with other members of the genus. The values of DNA-DNA relatedness between strain TBZ21T and the closely related strains H. fontilapidosi LMG 24455T and H. ventosae LMG 26187T were 42 ± 11% and 54 ± 16%, respectively. On the basis of phenotypic, chemotaxonomic and molecular characteristics, strain TBZ21T is concluded to represent a novel species of the genus Halomonas, for which the name Halomonas tabrizica sp. nov. is proposed. The type strain is TBZ21T (=LMG 25445T=DSM 23018T).