The Role of Extracellular Vesicles in Mediating Resistance to Anticancer Therapies.

Although advances in targeted therapies have driven great progress in cancer treatment and outcomes, drug resistance remains a major obstacle to improving patient survival. Several mechanisms are involved in developing resistance to both conventional chemotherapy and molecularly targeted therapies, including drug efflux, secondary mutations, compensatory genetic alterations occurring upstream or downstream of a drug target, oncogenic bypass, drug activation and inactivation, and DNA damage repair. Extracellular vesicles (EVs) are membrane-bound lipid bilayer vesicles that are involved in cell-cell communication and regulating biological processes. EVs derived from cancer cells play critical roles in tumor progression, metastasis, and drug resistance by delivering protein and genetic material to cells of the tumor microenvironment. Understanding the biochemical and genetic mechanisms underlying drug resistance will aid in the development of new therapeutic strategies. Herein, we review the role of EVs as mediators of drug resistance in the context of cancer.

The Role of Cancer-Associated Fibroblasts and Extracellular Vesicles in Tumorigenesis.

Extracellular vesicles (EVs) play a key role in the communication between cancer cells and stromal components of the tumor microenvironment (TME). In this context, cancer cell-derived EVs can regulate the activation of a CAF phenotype in TME cells, which can be mediated by several EV cargos (e.g., miRNA, proteins, mRNA and lncRNAs). On the other hand, CAF-derived EVs can mediate several processes during tumorigenesis, including tumor growth, invasion, metastasis, and therapy resistance. This review aimed to discuss the molecular aspects of EV-based cross-talk between CAFs and cancer cells during tumorigenesis, in addition to assessing the roles of EV cargo in therapy resistance and pre-metastatic niche formation.

Trends in the Prevalence of Hepatitis B Virus, Hepatitis C Virus, and HIV Infections in Iranian Patients with Hereditary Bleeding Disorders.

BACKGROUND: Patients with hereditary bleeding disorders (HBDs) have always been vulnerable to transfusion-transmitted infections (TTIs) such as hepatitis B virus (HBV), hepatitis C virus (HCV), and human immunodeficiency virus (HIV) infections due to being regular recipients of blood and blood products. This study aimed to detect the trends in the prevalence of HBV, HCV, and HIV infections by birthyear in Iranian patients with HBDs to show the efficacy of national interventions implemented to administrate control and to prevent these infections, i.e., blood safety, newborn HBV vaccination, and safe replacement treatments. METHODS: In this retrospective study, the trends in the prevalence of hepatitis B core antibody (HBcAb), HCV antibody (HCV-Ab), and HIV antibody (HIV-Ab) in Iranian patients with HBDs born before 2012 were assessed using patients' clinical archives. The determinants of HBV, HCV, and HIV infections were investigated in bivariable and multivariable logistic regression analyses. RESULTS: Out of 1475 patients with HBDs, most were male (87.7%) and diagnosed with hemophilia A (52.1%) and severe bleeding disorder (63.7%). The prevalence of HBcAb, HCV-Ab, and confirmed HIV-Ab was 22.9%, 59.8%, and 1.2%, respectively. The trends in HBcAb, HCV-Ab, and HIV-Ab were all decreasing by birthyear and reached a stable level of 0% for patients with birthyears in 1999, 2000, and 1984, respectively. In multivariable analysis, birthyear was significantly associated with HBcAb prevalence. In the multivariable analysis, type of HBD; birthyear; bleeding severity; histories of receiving packed cells, fresh frozen plasma, and cryoprecipitate before 1996; and history of receiving factor concentrate before 1997 were highly associated with the prevalence of HCV-Ab. Moreover, in the bivariable analysis, birthyear and type of HBD were associated with HIV-Ab prevalence. CONCLUSION: This study demonstrated the decreasing trends in HBV, HCV, and HIV seroprevalence in Iranian patients with HBDs following preventive interventions such as HBV vaccination, blood safety measures, and the provision of safe replacement treatments.

Humans in the upstream can exacerbate climate change impacts on water birds' habitat in the downstream.

The present paper aims to quantify how human-made changes in the upstream exacerbate climate change impacts on water birds' habitat in the downstream. To reduce climate change effects and design adaptation policies, it is important to identify whether human activities understate or overstate the effects of climate change in a region on its inhabitants. This paper also shows how human activities may magnify climate change impacts both locally and regionally. Land-use/land-cover change as the important sign of human-made destruction in an ecosystem was detected in the upstream of the Helmand basin over 40 years. Owing to conflicts in Afghanistan, studies on this basin are rare. The water bird's habitat suitability maps during the study period were created using the maximum entropy model and the multi-criteria evaluation method. The post-classification method was applied to show the land-use/land-cover change over 40 years. These results were compared to the area of suitable habitat for water birds. The findings of these analyses indicated that the irrigated farming was expanded in the upstream despite climate change and water limitation, while the water birds' habitat in the downstream was declined. These results revealed that the unsustainable pattern of farming and blocking water behind dams in the upstream exacerbated the negative effects of climate change on water birds' habitat in the downstream. The significance of this study is to demonstrate the role of human in exacerbating climate change impacts both locally and regionally.

An investigation into climatic and terrestrial drivers of dust storms in the Sistan region of Iran in the early twenty-first century.

Dust storms cause a wide range of impacts on environment, economy and human health in the Sistan region of southeastern Iran. This paper investigates long-term variability of dust activity over 23 years (1997-2019) using the Dust Storm Index (DSI) and the frequency of dust-storm days (DSD, visibility <1000 m) and assesses the associated importance of various terrestrial and climatic drivers. A dust storm corridor was identified, based on the prevailing wind direction at Zabol, including parts of the Hamoun lakes and surrounding desert in order to study the effects of vegetation cover and lake water levels on dust activity. The results show maximum intensity of dust storms occurred at 10:30 a.m. and in the summer, consistent with the highest wind speeds - associated with the regionally important Levar wind - and highest air temperatures and lowest precipitation and relative humidity. Strong positive correlations were demonstrated between DSI and wind speed, particularly in summer. The 2000-2004 period saw severe dust-raising activity with a DSI of 530.6. Mean wind speeds were greater and precipitation, humidity, vegetation and water coverage were lower during this severe dust-activity period than in other periods. Comparing 2000-2004 with 1997-1999, DSI was five times higher and DSD eight times higher. The dust storms with the longest duration occurred in July 2001 and June 2008 (114 h and 78 h respectively). The July 2001 event, in which wind speed peaked at 25 m/s and visibility dropped to 100 m on several occasions, may be the longest continuous dust storm on record. The key role of water and vegetation cover in the Hamouns was highlighted, indicating the importance of protecting the Hamoun ecosystems and sustainably managing their water resources in efforts to mitigate dust storm hazards in the Sistan region.

Prevalence of hepatitis C virus NS5A resistance-associated substitutions in chronic infection with genotype 1: A pooled analysis based on deposited sequences in GenBank.

INTRODUCTION: Resistance-associated substitutions (RASs) in the NS5A gene of hepatitis C virus (HCV) has been studied as one of the predictors of response to NS5A inhibitor-containing regimens. This study aimed to evaluate the prevalence of pre-treatment naturally-occurring NS5A RASs in HCV isolates from patients with chronic HCV genotype 1 (HCV-1) infection retrieved from GenBank. METHODS: In the search procedure, the studies with published HCV-1 NS5A sequence in GenBank were screened and evaluated for inclusion in the pooled analysis. The sequences of the included studies were retrieved from GenBank and evaluated for substitutions in amino acid positions24, 26, 28, 29, 30, 31, 32, 38, 58, 62, 92 and 93 of HCV NS5A including RASs and RASs conferring >100 resistance fold change (RASs >100X). RESULTS: In the pooled analysis, 2409 isolates from patients with HCV-1 infection were included, consisting 1305 (54.2%) HCV-1a and 1104 (45.8%) HCV-1b isolates. The prevalence of NS5A RASs and RASs >100X were 16.0% (95%CI = 14.6%-17.5%) and 4.7% (95%CI = 3.9%-5.6%), respectively. The NS5A RASs were more frequently observed in HCV-1b isolates than in HCV-1a isolates (P < 0.001). CONCLUSION: The naturally-occurring HCV NS5A RASs especially those with clinical relevance (RASs >100X) are observed in a small (4.7%) number of patients with HCV-1 infection.