To our knowledge, this is the first study illustrating the mechanistic role of Pak1 in causing gemcitabine resistance via multiple signaling crosstalks, and hence Pak1-specific inhibitors will prove to be a better adjuvant with existing chemotherapy modality for PDAC.
Evidence-based medicine (EBM) has brought a substantial change in medical practice and clinical care approach (1-3). It has helped to focus on valid and reliable information to make sound decisions in the area of disease management. Although randomized controlled trials (RCTs) are considered as the reference standard and provide valuable evidence about the efficacy of new treatments, yet they do not answer all important questions about the specific treatment. Most of the knowledge in clinical practice comes from observational studies from which we can gain further experience to plan interventional studies in regards to efficacy, safety and tolerability of approved medicines (4). An observational study is defined as a study that provides estimates and examines associations of events in their natural settings without recourse to experimental intervention (5). It includes cohort studies (CO) ñ prospective and retrospective, crosssectional studies (CS), and case-control studies (CC) (6). Current evidence suggests that observational studies, such as those discussed earlier, both com
In this study, we have identified one microRNA, microRNA 493 (miR-493), which could simultaneously and directly regulate multiple genes downstream of the insulin-like growth factor 1 receptor (IGF1R) pathway, including IGF1R, by binding with complementary sequences in the 3' untranslated region (UTR) of mRNAs of IGF1R, insulin receptor substrate 1 (IRS1), and mitogen-activated protein kinase 1 (MAPK1), thereby potentiating their inhibitory function at multiple levels in development and progression of cancers. This binding was further confirmed by pulldown of miR with AGO-2 antibody. Further, results from head and neck samples showed that miR-493 levels were significantly downregulated in tumors, with a concomitant increase in the expression of IGF1R and key downstream effectors. Functional studies from miR-493 overexpression cells and nude-mouse models revealed the tumor suppressor functions of miR-493. Regulation studies revealed that Snail binds to the miR-493 promoter and represses it. We found the existence of a dynamic negative feedback loop in the regulation of IGF1R and miR-493 mediated via Snail. Our study showed that nicotine treatment significantly decreases the levels of miR-493-with a concomitant increase in the levels of Snail-an indication of progression of cells toward tumorigenesis, reestablishing the role of tobacco as a major risk factor for head and neck cancers and elucidating the mechanism behind nicotine-mediated tumorigenesis.
Background: Discovery of antibiotics have helped to manage the devastating diseases. Presently, the antibiotic era is threatened by the emergence of high level of antibiotic resistance of important pathogens. Misuse of antibiotics poses a serious risk to infectious disease control. It is necessary to improve public awareness to bring a change in the behavior of consumers. Therefore, present study was undertaken to assess the existing knowledge, attitude and practices related to antibiotic usage among university students.Methods: A cross-sectional study was carried out among students from Mumbai University, India during May-June 2017. 300 students were approached to participate in the study of which 250 agreed to participate (males: 117; females: 133). Pretested questionnaire was distributed and collected data was analyzed using IBM SPSS version 23.Results: Substantial number (33% and 40%) participants were unaware about the differences in antibiotic-anti-inflammatory drugs and antibiotic-antipyretics respectively. 28% of the participants thought it is right to stop antibiotics only based on symptoms improvement. Sixty eight percent and seventy nine percent participants believed that antibiotics should always be prescribed to treat flu like symptoms and pneumonia respectively.Conclusions: Participants demonstrated poor knowledge about antibiotics. Similarly, their attitude and practice toward antibiotic use was associated with misconceptions. An educational intervention can be introduced to make them aware about rational antibiotic practices.
Background: Self-medication, practiced globally is an important public health problem. Research studies have indicated inappropriate self‐medication results in adverse drug reactions, disease masking, antibiotic resistance and wastage of healthcare resources. The objectives of the study were to explore overall self-medication and antibiotic self-medication prevalence among students of university students in Karachi, Pakistan along with probable reasons, indications, and sources of advice for self-medication.Methods: A descriptive, cross-sectional, questionnaire-based study was carried out among students from university of Karachi, Pakistan during the time period of September to November 2016. Pretested questionnaire was distributed to 320 students, collected data was analyzed using IBM SPSS version 24.Results: From 320 students, 311 (83 male and 228 female) students participated in the study giving a response rate of 97%. Prevalence of self-medication was 66%. Belonging to higher monthly family income group was associated with likelihood of self-medication. Antibiotic self-medication prevalence was 39%. Lack of time (39%), and old prescription (35%) were the main reasons for self-medication. Pharmacy shop (75%) was the main source for self-medication. In case of antibiotics, 44% students changed the dosage of antibiotic and 50% students stopped antibiotics after the disappearance of the symptoms.Conclusions: Antibiotic self-medication (39%) and self-medication with other drugs among university students of Karachi is a worrisome problem. Our findings highlight the need for planning interventions to promote the judicious use of general medicines as well as that of antibiotics.
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