The role of Th-17 cells and IL-17 in the metastatic spread of breast cancer: As a means of prognosis and therapeutic target.

Metastatic breast cancer is one of the most common and well-known causes of death for women worldwide. The inflammatory tumor cell and other cancer hallmarks dictate the metastatic form and dissemination of breast cancer. Taking these into account, from various components of the tumor microenvironment, a pro-inflammatory infiltrative cell known as Th-17 plays an immense role in breast cancer proliferation, invasiveness, and metastasis. It has been demonstrated that IL-17, a pleiotropic pro-inflammatory cytokine generated by Th-17, is upregulated in a metastatic form of breast cancer. Recent research updates stated that chronic inflammation and mediators like cytokines and chemokines are causative hallmarks in many human cancers, including breast cancer. Therefore, IL-17 and its multiple downward signaling molecules are the centers of research attention to develop potent treatment options for cancer. They provide information on the role of IL-17-activated MAPK, which results in tumor cell proliferation and metastasis via NF-kB-mediated expression of MMP signaling. Overall, this review article emphasizes IL-17A and its intermediate signaling molecules, such as ERK1/2, NF-kB, MMPs, and VEGF, as potential molecular targets for the prevention and treatment of breast cancer.

Knowledge and Practice Toward Prevention of SARS-CoV-2 Among Healthcare Workers at Delghi Primary Hospital During a Massive Test Campaign in Northwest Gondar, Ethiopia: Institution-Based Descriptive Cross-Sectional Survey.

BACKGROUND: Since December 29, 2019, severe acute respiratory syndrome coronavirus (SARS-CoV-2) has been spreading and is associated with notoriously increased morbidity and mortality of populations worldwide, including Ethiopia. Medicine and the healthcare system have been challenged by both first and second-waves of SARS-CoV-2. During this entire crisis, the main purpose of this study was to determine the current evidence on the level of awareness and prevention practice of healthcare workers (HCWs) at the district primary hospital, Delghi Primary Hospital (DPH) regarding COVID-19 in the overall effort to control the spread of the virus. METHODS: Institutional-based descriptive cross-sectional analysis was performed between late August and September 20, 2020. Participants of the study were HCWs with various occupations at DPH, North West Gondar, Ethiopia. In this study, among 112 health professions, we included a total of 104 HCWs. Written consent was obtained for willingness of the study participants from the DPH administrative office. Then, using a pre-tested, structured, and self-administered questionnaire, data were collected. The questionnaire included socio-demographics, sources of information, knowledge, and practice measures regarding COVID-19. The collected data were analyzed through IBM SPSS version 20. As a cut-off value, ≥8 out of 15 knowledge questions and ≥7 out of 14 practice questions were considered good knowledge and practice, respectively. RESULTS: The result of this study showed the majority of the respondents were male (71/104, (68.3%)), with a median age of 28 (minimum age 20 and maximum age 50) years. Thus, 94.2% (n=98/104) was the overall rate of correctly answered questions out of 15 knowledge questions. However, 40.6% of them had poor prevention practices. 73.1% of participants used regular hand-washing with soap and 64.4% used hand sanitizer and handshake avoidance equally for prevention purposes. Whereas, social distancing rule and mask-wearing were reported as impracticable by 55.8% and 44.2%, respectively. CONCLUSION: 94.2% of HCWs had a good level of knowledge about COVID-19; in contrast, lack of preventive practice was observed. This implies that there is a gap between knowledge and implementation of preventive measures toward the disease.

Helminth Induced Immunoregulation and Novel Therapeutic Avenue of Allergy.

Allergic diseases are increasing at an alarming rate worldwide, particularly in developed countries. In contrast, there is a decrease in the prevalence of helminthic infections and other neglected diseases. The hygiene hypothesis elaborates parasitic infection, and allergy-associated diseases have an inverse relationship. Acute helminthic infection and allergic reaction stimulate Type 2 helper cells (Th2) immune response with up-regulation of cytokines IL-4-, IL-5-, and IL-13-mediated IgE and mast cell production, as well as eosinophilia. However, people who chronically suffer from helminthic infections are demarcated through polarized Th2 resulting in alternative macrophage activation and T regulatory response. This regulatory system reduces allergy incidence in individuals that are chronically diseased through helminth. As a result, the excretory-secretory (ES) substance derived from parasites and extracellular vesicular components can be used as a novel therapeutic modality of allergy. Therefore, the aim of this review meticulously explored the link between helminth infection and allergy, and utilization of the helminth secretome for therapeutic immunomodulation.

Inflammation Mediated Hepcidin-Ferroportin Pathway and Its Therapeutic Window in Breast Cancer.

Experimental and clinical data strongly support that iron is an essential element which plays a big role in cancer biology. Thus, hepcidin (Hp) and ferroportin (Fpn) are molecules that regulate and maintain the metabolism of iron. A peptide hormone hepcidin limits recycled and stored iron fluxes in macrophage and hepatic hepatocyte, respectively, to the blood stream by promoting degradation of the only iron exporter, Fpn, in the target cells. Moreover, the inflammatory microenvironment of breast cancer and altered hepcidin/ferroportin pathway is intimately linked. Breast cancer exhibits an iron seeking phenotype that is accomplished by tumor-associated macrophage (TAM). Because macrophages contribute to breast cancer growth and progression, this review will discuss TAM with an emphasis on describing how TAM (M2Ф phenotypic) interacts with their surrounding microenvironment and results in dysregulated Hp/Fpn and pathologic accumulation of iron as a hallmark of its malignant condition. Moreover, the underlying stroma or tumor microenvironment releases significant inflammatory cytokines like IL-6 and bone morphogenetic proteins like BMP-2 and 6 leading in aberrant Hp/Fpn pathways in breast cancer. Inflammation is primarily associated with the high intracellular iron levels, deregulated hepcidin/ferroportin pathway, and its upstream signaling in breast cancer. Subsequently, scholars have been reported that reducing iron level and manipulating the signaling molecules involved in iron metabolism can be used as a promising strategy of tumor chemotherapy. Here, we review the key molecular aspects of iron metabolism and its regulatory mechanisms of the hepcidin/ferroportin pathways and its current therapeutic strategies in breast cancer.

Role of IFN and Complements System: Innate Immunity in SARS-CoV-2.

The critical role of the innate immune system has been confirmed in driving local and systemic inflammation and the cytokine release storm in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). This dysregulated immune response is focused on interferon (IFN) and complement activation, which are crucial for the development of metabolic inflammation, local lung tissue damage, and systemic multi-organ failure. IFNs control viral infections by inducing expression of IFN-stimulated genes (ISGs) that restrict distinct steps of viral replication. Therefore, in this review article, we propose the mechanism of SARS-CoV-2-associated acute respiratory disease syndrome, and assess treatment options by considering IFNs and by targeting IFN-antagonist SARS-CoV-2 virulent gene products. Furthermore, we elaborate on the mechanism of the amplified complement-mediated inflammatory cytokine storm, and propose an antiviral and immunotherapeutic strategy against coronavirus disease 2019 (COVID-19).