Heterologous expression, purification, and refolding of SRY protein: role of L-arginine as analyzed by simulation and practical study.

Escherichia coli is a widely-used cell factory for recombinant protein production, nevertheless, high amount of produced protein is seen in aggregated form. The purpose of this study was to improve the solubility of recombinant bovine sex-determining region Y protein (rbSRY) by exploring the effect of temperature, inducer, and water-arginine mixed solvent. Codon-optimized rbSRY expressed in Rosetta-gami B (DE3) pLysS and purified by NI-NTA His-select affinity chromatography in the native and denaturing conditions. A three-dimensional model of SRY was built and studied through molecular dynamics simulations in water and in the presence of L-arginine as co-solvent. Results indicated the significant effects of temperature and IPTG concentration (P < 0.001) on the solubility of rbSRY. The binding activity of native, inclusion bodies and refolded fractions to anti-rbSRY monoclonal antibody were concentration-dependent (P < 0.001). Based on molecular modeling results, the propensity of fragments in the N-terminal domain to form ß-sheet and the relative instability of α-helices in terminal domains are the probable reasons for the high aggregation potential of SRY, which are mitigated in the presence of L-arginine. Altogether, our rbSRY protein was properly produced and applying appropriate culture conditions could help enhance its solubility, refold inclusion bodies, and improve its activity upon refolding.

Attitudes of medical students towards incentives offered by pharmaceutical companies -- perspective from a developing nation -- a cross-sectional study.

BACKGROUND: A training physician has his first interaction with a pharmaceutical representative during medical school. Medical students are often provided with small gifts such as pens, calendars and books, as well as free lunches as part of drug promotion offers. Ethical impact of these transactions as perceived by young medical students has not been investigated in Pakistan before. This study aimed to assess the association of socio-demographic variables with the attitudes of medical students towards pharmaceutical companies and their incentives. METHODS: As part of a cross-sectional survey, a validated questionnaire previously used for assessing attitude of medical students towards pharmaceutical industry, was modified, pre-tested and distributed among consenting clinical year students at DUHS and AKU. Questions included acceptability of pharmaceutically sponsored gifts, events and tuition fee, and their impact on future prescription. Responses were graded as agree, disagree or neutral which were then scored according to the AMSA guidelines of ethical conduct. RESULTS: Out of a total of 353 targeted students 303 responded, corresponding to a response rate of 85.8%. Responses indicated that 42.7% students believed in no interaction with drug companies during medical school. However, 81% of students favored pharmaceutical sponsorship of student-body events/seminars at medical colleges. More than one-third of the students were comfortable receiving gifts from drug companies. Overall, the results of this study offer an interesting comparison between the students of a private medical school (AKU) and a public medical school (DUHS); AKU students exhibited a greater degree of mistrust towards drug information provided by pharmaceutical companies compared to DUHS students (p = 0.040). Furthermore, when asked if there was a need to incorporate guidelines in the undergraduate curriculum with regard to interaction with drug companies, 84.2% students at AKU agreed, compared to 54.9% at DUHS. Medical student Attitude Scores are more or less similar to each other independent of their various demographical differences. CONCLUSION: This study highlights that medical students in our population have a high level of acceptability towards incentives offered by pharmaceutical industry and that formal guidance regarding the subject should be incorporated into medical curriculum.

Autophagy: A challengeable paradox in cancer treatment.

OBJECTIVE: Autophagy is an intracellular degradation pathway conserved in all eukaryotes from yeast to humans. This process plays a quality-control role by destroying harmful cellular components under normal conditions, maintaining cell survival, and establishing cellular adaptation under stressful conditions. Hence, there are various studies indicating dysfunctional autophagy as a factor involved in the development and progression of various human diseases, including cancer. In addition, the importance of autophagy in the development of cancer has been highlighted by paradoxical roles, as a cytoprotective and cytotoxic mechanism. Despite extensive research in the field of cancer, there are many questions and challenges about the roles and effects suggested for autophagy in cancer treatment. The aim of this study was to provide an overview of the paradoxical roles of autophagy in different tumors and related cancer treatment options. METHODS: In this study, to find articles, a search was made in PubMed and Google scholar databases with the keywords Autophagy, Autophagy in Cancer Management, and Drug Design. RESULTS: According to the investigation, some studies suggest that several advanced cancers are dependent on autophagy for cell survival, so when cancer cells are exposed to therapy, autophagy is induced and suppresses the anti-cancer effects of therapeutic agents and also results in cell resistance. However, enhanced autophagy from using anti-cancer drugs causes autophagy-mediated cell death in several cancers. Because autophagy also plays roles in both tumor suppression and promotion further research is needed to determine the precise mechanism of this process in cancer treatment. CONCLUSION: We concluded in this article, autophagy manipulation may either promote or hinder the growth and development of cancer according to the origin of the cancer cells, the type of cancer, and the behavior of the cancer cells exposed to treatment. Thus, before starting treatment it is necessary to determine the basal levels of autophagy in various cancers.

Treatment of persistent chemotherapy-induced hair loss (Alopecia) with human mesenchymal stromal cells exosome enriched extracellular vesicles: A case report.

Introduction: Cancer is among the leading causes of death worldwide and affects a considerable number of individuals. Chemotherapy is one the most common treatment for this condition and hair loss is among one of the most prevalent side effects. In this study, we report successful treatment of a patient suffering from persistent chemotherapy-induced alopecia (PCIA) with extracellular enriched vesicles (EVs) derived from human placental mesenchymal stromal cells (MSCs). Case presentation: The patient was a 36-year-old woman with a history of invasive ductal carcinoma, underwent six courses of chemotherapy with paclitaxel and adriamycin. Following this treatment and for almost 18 months, she, unfortunately, had no regrowth of hair except some light vellus hairs on the scalp. She then received MSC-derived EVs with scalp injection (subcutaneous) every 4 weeks for 3 continuous months at which point she presented complete regrowth of terminal hair on her scalp. Conclusion: This report demonstrates that MSC-derived EVs could be a possible treatment for permanent chemotherapy-induced alopecia; however, further studies and trials are necessary.

Cell line-directed breast cancer research based on glucose metabolism status.

Metabolic reprogramming is a potential hallmark of tumor cells to support continuous proliferation. Metabolic heterogeneity in breast cancer patients has been highlighted as the driving cause of tumor progression and resistance to anticancer drugs. Studying and identifying distinct metabolic alterations in breast cancer subtypes could offer new perspectives for faster diagnosis and treatment. Given cancer cell dependency on glycolysis, the primary energy source, this enzymatic pathway will play a critical role in targeting therapies. Knowledge about the specific metabolic dependencies of tumors for growth and proliferation can be promising for novel targeted and cell-based therapies. Here, the metabolic status with emphasis on glycolysis of breast cancer cell lines according to their classification was reviewed.

Perfluorocarbon as an adjuvant for tumor anti-angiogenic therapy: Relevance to hypoxia and HIF-1.

Lack of vascularization results in increased demand for oxygen and creates a defined feature of the tumor microenvironment known as tumor hypoxia. It is well established that in response to hypoxia, hypoxia-inducible factor-1 α (HIF-1α) is induced which is an important factor in angiogenesis, invasion and metastasis. In turn, HIF-1α regulates the expression of angiogenic factors, such as vascular endothelial growth factor (VEGF). Ascribed to abnormal characteristics of tumor angiogenic networks, antiangiogenic therapy approaches can even worsen the hypoxic condition and can create cancer cells with stemness features. Hence oxygen delivery via perfluorocarbon (PFC) to hypoxic sites seems to result in unstable HIF expression and consequent inactivation of angiogenesis cascade and metastasis and therefore, inhibition of cancer cells stemness.

Artificial Intelligence and COVID-19: Deep Learning Approaches for Diagnosis and Treatment.

COVID-19 outbreak has put the whole world in an unprecedented difficult situation bringing life around the world to a frightening halt and claiming thousands of lives. Due to COVID-19's spread in 212 countries and territories and increasing numbers of infected cases and death tolls mounting to 5,212,172 and 334,915 (as of May 22 2020), it remains a real threat to the public health system. This paper renders a response to combat the virus through Artificial Intelligence (AI). Some Deep Learning (DL) methods have been illustrated to reach this goal, including Generative Adversarial Networks (GANs), Extreme Learning Machine (ELM), and Long/Short Term Memory (LSTM). It delineates an integrated bioinformatics approach in which different aspects of information from a continuum of structured and unstructured data sources are put together to form the user-friendly platforms for physicians and researchers. The main advantage of these AI-based platforms is to accelerate the process of diagnosis and treatment of the COVID-19 disease. The most recent related publications and medical reports were investigated with the purpose of choosing inputs and targets of the network that could facilitate reaching a reliable Artificial Neural Network-based tool for challenges associated with COVID-19. Furthermore, there are some specific inputs for each platform, including various forms of the data, such as clinical data and medical imaging which can improve the performance of the introduced approaches toward the best responses in practical applications.

Autophagy, cancer and angiogenesis: where is the link?

BACKGROUND: Autophagy is a catabolic process for degradation of intracellular components. Damaged proteins and organelles are engulfed in double-membrane vesicles ultimately fused with lysosomes. These vesicles, known as phagophores, develop to form autophagosomes. Encapsulated components are degraded after autophagosomes and lysosomes are fused. Autophagy clears denatured proteins and damaged organelles to produce macromolecules further reused by cells. This process is vital to cell homeostasis under both physiologic and pathologic conditions. MAIN BODY: While the role of autophagy in cancer is quite controversial, the majority of studies introduce it as an anti-tumorigenesis mechanism. There are evidences confirming this role of autophagy in cancer. Mutations and monoallelic deletions have been demonstrated in autophagy-related genes correlating with cancer promotion. Another pathway through which autophagy suppresses tumorigenesis is cell cycle. On the other hand, under hypoxia and starvation condition, tumors use angiogenesis to provide nutrients. Also, autophagy flux is highlighted in vessel cell biology and vasoactive substances secretion from endothelial cells. The matrix proteoglycans such as Decorin and Perlecan could also interfere with angiogenesis and autophagy signaling pathway in endothelial cells (ECs). It seems that the connection between autophagy and angiogenesis in the tumor microenvironment is very important in determining the fate of cancer cells. CONCLUSION: Matrix glycoproteins can regulate autophagy and angiogenesis linkage in tumor microenvironment. Also, finding details of how autophagy and angiogenesis correlate in cancer will help adopt more effective therapeutic approaches.

Imaging and intervention of paraneoplastic effect of a right atrial myxoma on factor VII activity levels.

We present the case of a 64-year-old Pakistani man with right atrial myxoma, recently diagnosed with acquired severe factor VII (FVII) deficiency. The patient presented with a history of chronic hiccups and weight loss. Initial evaluation revealed an isolated prolonged prothrombin time, severely reduced FVII activity level, and a giant right atrial myxoma protruding into the right ventricle on computed tomographic thorax and echocardiography. After surgical resection, the patient maintained normal prothrombin time with increased FVII activity level in the immediate 24 hours postoperatively, and a dramatically high level of FVII activity at the 2-month follow-up. We believe that the paraneoplastic effect of myxoma on the FVII activity levels is previously unreported. In addition, we believe that hiccups as a presenting symptom for a myxoma with an atypical origin from the lateral wall of the right atrium has not been reported.