Current approaches for combination therapy of cancer: The role of immunogenic cell death

Cell death resistance is a key feature of tumor cells. One of the main anticancer therapies is increasing the susceptibility of cells to death. Cancer cells have developed a capability of tumor immune escape. Hence, restoring the immunogenicity of cancer cells can be suggested as an effective approach against cancer. Accumulating evidence proposes that several anticancer agents provoke the release of danger-associated molecular patterns (DAMPs) that are determinants of immunogenicity and stimulate immunogenic cell death (ICD). It has been suggested that ICD inducers are two different types according to their various activities. Here, we review the well-characterized DAMPs and focus on the different types of ICD inducers and recent combination therapies that can augment the immunogenicity of cancer cells

Neutrophils, Crucial, or Harmful Immune Cells Involved in Coronavirus Infection: A Bioinformatics Study

The latest member of the Coronaviridae family, called SARS-CoV-2, causes the Coronavirus Disease 2019 (COVID-19). The disease has caused a pandemic and is threatening global health. Similar to SARS-CoV, this new virus can potentially infect lower respiratory tract cells and can go on to cause severe acute respiratory tract syndrome, followed by pneumonia and even death in many nations. The molecular mechanism of the disease has not yet been evaluated until now. We analyzed the GSE1739 microarray dataset including 10 SARS-positive PBMC and four normal PBMC. Co-expression network analysis by WGCNA suggested that highly preserved 833 turquoise module with genes were significantly related to SARS-CoV infection. ELANE, ORM2, RETN, BPI, ARG1, DEFA4, CXCL1, and CAMP were the most important genes involved in this disease according to GEO2R analysis as well. The GO analysis demonstrated that neutrophil activation and neutrophil degranulation are the most activated biological processes in the SARS infection as well as the neutrophilia, basophilia, and lymphopenia predicted by deconvolution analysis of samples. Thus, using Serpins and Arginase inhibitors during SARS-CoV infection may be beneficial for increasing the survival of SARS-positive patients. Regarding the high similarity of SARS-CoV-2 to SARS-CoV, the use of such inhibitors might be beneficial for COVID-19 patients

The effect of cations on sperm motility performance and fertilizing ability of silver carp Hypophtalmychtis molitrix

The objective of the study was to investigate the effect of saline solution containing cations (Na+, K+, Ca+2, Mg+2) on sperm motility performance (duration of sperm motility and percentage of motile spermatozoa) and fertilizing capacity of sperm (fertilization rate, hatching rate, larvae length during hatching, larvae length during active feeding and survival rate) in silver carp. The results suggested that solutions containing ions did not improve the duration of sperm motility. The same was observed for the percentage of motile spermatozoa. Fertilization rate influenced by solutions containing Ca+2, and other ions could not affect this parameter. The results showed that hatching rate was higher in solutions containing 99 mEq/L NaCl, 2 mEq/L MgCl2 and 2, 4 mEq/L CaCl2 respectively. Also, survival rate was higher in the solution containing 2 mEq/L MgCl2 and 36 mg/dL KCl respectively.With regard to the obtained results, it was concluded that using appropriate activation medium can improve quality of fish sperm and subsequently increases artificial reproduction performance

Knowledge and practice of foot care in Iranian people with type 2 diabetes

The aim of this study was to determine the knowledge and practice of foot care in people with type 2 diabetes. We carried out a cross-sectional study. A questionnaire was completed by 148 patients with type 2 diabetes in Tehran, Iran. Knowledge score was calculated and the current practice was determined. The mean knowledge score was 6.6 (standard deviation ±3.0) out of a possible 16. Illiterate patients were the least knowledgeable (P = 0.008). Lack of adequate knowledge includes the following: 56 not aware of the effect of smoking on the circulation to the feet, 60 failed to inspect their feet and 42 did not know to trim their toenails. High risk practices including use of irritants to water (66.5) and walking barefoot (62). The results of this study highlight the patients' inadequate knowledge of self-care about their foot and lack of optimal podiatry service in Iran. These findings have implications for further evaluation, planning and management of patient care in diabetic foot disease. © 2007 Blackwell Publishing Ltd and Medicalhelplines.com Inc

From Melanoma Development to RNA-Modified Dendritic Cell Vaccines: Highlighting the Lessons From the Past

Although melanoma remains the deadliest skin cancer, the current treatment has not resulted in the desired outcomes. Unlike chemotherapy, immunotherapy has provided more tolerable approaches and revolutionized cancer therapy. Although dendritic cell-based vaccines have minor side effects, the undesirable response rates of traditional approaches have posed questions about their clinical translation. The immunosuppressive tumor microenvironment can be the underlying reason for their low response rates. Immune checkpoints and indoleamine 2,3-dioxygenase have been implicated in the induction of immunosuppressive tumor microenvironment. Growing evidence indicates that the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase/Protein kinase B (PKB) (PI3K/AKT) pathways, as the main oncogenic pathways of melanoma, can upregulate the tumoral immune checkpoints, like programmed death-ligand 1. This study briefly represents the main oncogenic pathways of melanoma and highlights the cross-talk between these oncogenic pathways with indoleamine 2,3-dioxygenase, tumoral immune checkpoints, and myeloid-derived suppressor cells. Moreover, this study sheds light on a novel tumor antigen on melanoma, which has substantial roles in tumoral immune checkpoints expression, indoleamine 2,3-dioxygenase secretion, and stimulating the oncogenic pathways. Finally, this review collects the lessons from the previous unsuccessful trials and integrates their lessons with new approaches in RNA-modified dendritic cell vaccines. Unlike traditional approaches, the advances in single-cell RNA-sequencing techniques and RNA-modified dendritic cell vaccines along with combined therapy of the immune checkpoint inhibitors, indoleamine 2,3-dioxygenase inhibitor, and RNA-modified dendritic cell-based vaccine can overcome these auto-inductive loops and pave the way for developing robust dendritic cell-based vaccines with the most favorable response rate and the least side effects

Qualitative Analysis of the Content Found in Online Discussion Boards for Urethral Stricture Disease and Urethroplasty.

ObjectiveTo describe the patient experience and chief concerns with urethroplasty to improve physician understanding and patient education. Online discussion boards allow patients with urethral stricture disease (USD) to connect with other USD patients. It is unknown how men use these web resources and what information is available about urethroplasty.MethodsThree online forums featuring urethroplasty were identified by Google search. Thematic analysis categorized the content of posts using manually applied codes, with inter-rater reliability and descriptive statistics generated by Dedoose (Los Angeles, CA).ResultsA total of 140 unique posters contributed 553 posts to the forums. Posts were categorized as information support (n = 651), issues posturethroplasty (n = 470), own experience preurethroplasty (n = 336), feelings towards other posters (n = 312), what to expect posturethroplasty (n = 265), feelings after urethroplasty (n = 228), and considerations before urethroplasty (n = 134). Experience navigating the healthcare system with USD (n = 141) and weak urine stream (n = 70) were the most frequent preurethroplasty complaints. Postoperative pain (n = 164) was the most frequent issue. Patients expressed more positivity (n = 126) and satisfaction (n = 120) than negativity (n = 33) with urethroplasty.ConclusionPatients participated in online discussions to share experiences with USD and urethroplasty, receive emotional support, and find answers. Men were more often satisfied than not with their urethroplasty outcomes, with 88% of postoperative feelings coded as positive or satisfied compared to negative. This study provides physicians with insight into the experiences of patients and how to best educate them

Pancreatic cancer signaling pathways, genetic alterations, and tumor microenvironment: The barriers affecting the method of treatment

Genetic alterations, especially the K-Ras mutation, carry the heaviest burden in the progression of pancreatic precursor lesions into pancreatic ductal adenocarcinoma (PDAC). The tumor microenvironment is one of the challenges that hinder the therapeutic approaches from functioning sufficiently and leads to the immune evasion of pancreatic malignant cells. Mastering the mechanisms of these two hallmarks of PDAC can help us in dealing with the obstacles in the way of treatment. In this review, we have analyzed the signaling pathways involved in PDAC development and the immune system’s role in pancreatic cancer and immune checkpoint inhibition as next-generation therapeutic strategy. The direct targeting of the involved signaling molecules and the immune checkpoint molecules, along with a combination with conventional therapies, have reached the most promising results in pancreatic cancer treatment

A controlled trial of the effectiveness of a diabetes education programme in a multi-ethnic community in Glasgow [ISRCT28317455]

BACKGROUND: Epidemiologic data have shown that the prevalence of Type 2 diabetes varies with ethnic origin. Type 2 diabetes is up to four times more common in British South Asians than in the indigenous white population. The aim of this study was to develop a culturally appropriate educational intervention programme for South Asians with Type 2 diabetes. We then investigated whether this intervention could produce an improvement, and finally whether any improvement was greater than background changes in knowledge in comparison groups. METHODS: A multi-site prospective, randomised controlled study was conducted in all day care centres and three general practice registers with high proportion patients from different ethnic minority groups in Glasgow, Scotland. The intervention consisted of 18 educational sessions in 6 separate programmes. A modified questionnaire was used to measure the knowledge, attitudes, and practice of diabetes before and after intervention. RESULTS: Baseline assessment showed that Indian and Pakistani subjects had less knowledge about diabetes, regarded the disease less seriously, and had a lesser understanding of the relationship between control and complications than the white population. No differences in initial responses were found between those who completed the second assessment and those who did not. The intervention group showed significant improvements in scores for Knowledge (+12.5%); Attitudes toward seriousness (+13.5%), complications (+8.1%), Practice (+20.0%). However there were also changes in the ethnic control group scores; respectively +5.0%, +16.3% (significant P < 0.001), +1.5%, +1.7%. The single white control group also showed some improvements; respectively +12.2%, +12.4% (P = 0.04), +6.0%, +25.0% (P = 0.007), but the differences in improvement between these two control groups were not significant. Overall, the improvement seen was similar in both intervention and ethnic control groups and there was no significant difference in the amount of change (P = 0.36 CI -0.9 to +2.6). CONCLUSION: This study has shown that conducting a culturally-competent educational intervention in patients with Type 2 diabetes from ethnic minority groups is feasible and can improve their knowledge and attitudes and practice. However there was no net benefit compared with the control group