Altholactone Displays Promising Antimicrobial Activity

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5-Fluorouracil-induced apoptosis in colorectal cancer cells is caspase-9-dependent and mediated by activation of protein kinase C-d

Elucidation of the molecular mechanisms by which 5-fluorouracil (5-FU) induces apoptosis is required in order to understand the resistance of colorectal cancer (CRC) cells to 5-FU. In the current study, 5-FU-induced apoptosis was assessed using the propidium iodide method. Involvement of protein kinase C (PKC) was assessed by evaluating the extent of their activation in CRC, following treatment with 5-FU, using biochemical inhibitors and western blot analysis. The results revealed that 5-FU induces varying degrees of apoptosis in CRC cells; HCT116 cells were identified to be the most sensitive cells and SW480 were the least sensitive. In addition, 5-FU-induced apoptosis was caspase-dependent as it appeared to be initiated by caspase-9. Furthermore, PKCe was marginally expressed in CRC cells and no changes were observed in the levels of cleavage or phosphorylation following treatment with 5-FU. The treatment of HCT116 cells with 5-FU increased the expression, phosphorylation and cleavage of PKCd. The inhibition of PKCd was found to significantly inhibit 5-FU-induced apoptosis. These results indicated that 5-FU induces apoptosis in CRC by the activation of PKCd and caspase-9. In addition, the levels of PKCd activation may determine the sensitivity of CRC to 5-FU

Primary health care policy and vision for community pharmacy and pharmacists in Jordan

Jordan is considered a low middle-income country with a population of 9.956 million in 2018. It is considered the training center for healthcare professions in the region, as the Jordanian healthcare sector has seen remarkable development. In 2017, the expenditure on health as a percentage of Gross Domestic Product (GDP) was estimated to be around 8%. The healthcare sector is divided into two main sectors; the public and the private sector with both including hospitals, primary care clinics and pharmacies. The Jordanian government has a strong commitment to health and educational programs; hence, an increase in the number of pharmacy schools and pharmacy graduates has occurred in the past few years. Health authorities, such as the Jordan Food and Drug Association (JFDA) and the Jordan Pharmaceutical Association (JPA) have played an important role in ensuring the availability and affordability of medications, and has influenced the practice of pharmacists. Protecting the pharmaceutical market and professional interests, preserving pharmacists' rights, building needed cooperation with the internal federation, and maintaining professional ethics are some of the objectives for the JPA. Hence, the integration of community pharmacists into the primary healthcare system is considered vital to the different health authorities in Jordan, emphasizing the fact that community pharmacists are the most trusted, accessible, and affordable healthcare providers in the country. There have been many developments in the pharmacy practice in the past recent years, including the establishment of ‘Good Pharmacy Practice’, new curricular development based on the international accreditation (the ACPE), a new immunization program, and health services research aimed to save patients’ lives, influence expenses, and improve patients’ quality of life. Although these developments in pharmacy practice are promising, challenges continue to exist, specifically the establishment of an evidence base for pharmaceutical care services such as the medication management review service

Inhibition of MEK sensitizes paclitaxel-induced apoptosis of human colorectal cancer cells by downregulation of GRP78

Here we report that paclitaxel induces variable degrees of apoptosis in human colorectal cancer cells. Paclitaxel induces multiple arms of the endoplasmic reticulum stress response, including upregulation of the 78-kDa glucose-regulatory protein (GRP78) and eukaryotic initiation factor [alpha] phosphorylation. Inhibition of the MEK/ERK pathway sensitized colorectal cancer cells to paclitaxel-induced apoptosis. A similar result was obtained by the inhibition of GRP78 using small interfering RNA molecules. Knockdown of MEK resulted in a significant downregulation of paclitaxel-induced upregulation of GRP78 indicating that activation of GRP78 is a downstream event of MEK/ERK pathway activation. These results indicate that GRP78 might be a novel mechanism underlying the resistance of colorectal cancer cells to microtubule-targeting drugs. A combination of compounds capable of suppressing GRP78 might be a golden approach for improving the effectiveness of taxanes

Involvement of endoplasmic reticulum stress in docetaxel-induced JNK-dependent apoptosis of human melanoma

Our previous studies revealed that Docetaxelinduced apoptosis of melanoma cells is entirely dependent on activation of the JNK signalling pathway. Here, we show that Docetaxel-induced apoptosis is mediated by induction of ER stress. This was shown by Docetaxelinduced activation of proteins involved in ER stress signalling namely GRP78, ATF6, IRE1α, and PERK/eIF2α. Knockdown of IRE1α by siRNA markedly inhibited Docetaxel-induced JNK activation and downstream targets of JNK indicating that activation of IRE1α was upstream of activation of the JNK. Co-immunoprecipitation experiments showed that activation of JNK is due to activation of ASK1 through formation of an IRE1α-TRAF2-ASK1 complex. ER stress mediated activation of the JNK pathway is downstream of activation of PKCδ in that downregulation of PKCδ expression using specific PKCδ siRNA significantly inhibited Docetaxel-induced activation of IRE1α and the JNK pathway. These findings provide new insights to understand the mode of action of taxanes in treatment of human melanoma

Awareness of pharmacy researchers about the national research code of ethics: A study from Jordan

Objective: In Jordan, research ethics have been subject to increasingly formal regulations and structuring. Recently the Ministry of Higher Education and Research Published the National Research Code of Ethics. However, little is known about the awareness of pharmacology researchers of this code and the extent of its applicability to their research. Methods: Purposeful sampling through institutions’ websites was used to identify staff members with excellent profiles from 20 Faculties of Pharmacy in Jordan. After obtaining the required approvals, in-depth interviews were conducted, recorded, transcribed, and analyzed using NVivo 11 Software. The interviews followed a previously prepared and validated interview guide that covered various aspects of education, research, and training. Key findings: Eighteen members of staff agreed to take part in the study. Qualitative analysis revealed three main themes each concerning respondents’ awareness of the National Code of Research Ethics in Jordan. The emerging themes were: the lack of awareness regarding the code of ethics, the need for clear guidelines for pharmacology research in Jordan, and the need for further workshops and training courses for pharmacology researchers. Conclusion: This study highlights a lack of awareness regarding the presence of the National Research Ethics Code among pharmacology researchers in Jordan. This might have negative implications on medical research. It was thought that the code of ethics should be incorporated in postgraduate pharmacy education, training courses for pharmacy researchers, and workshops for pharmacy academic staff

Methoxyphenylcipro induces antitumor activity in human cancer cells

To examine the antitumor activity of a new derivative of ciprofloxacin called methoxyphenylcipro (CMPP). Cell viability was assessed using the MTT assay and apoptotic cells and reactive oxygen species were evaluated using flow cytometry. Results revealed that CMPP induces antiproliferative activity against breast cancer cells and melanoma and to a lesser extent against colorectal cancer cells. Interestingly, compared to ciprofloxacin, CMPP-induced a selective cytotoxicity against human cancer cells but not human normal fibroblasts. The potential of CMPP to inhibit cellular growth in MD-MB-486 breast cancer cells and MV3 melanoma cells was largely due to induction of caspase-dependent apoptosis, as confirmed by caspase-3 activation and cleavage of its substrate PARP. In addition, results indicated that CMPPinduced apoptosis is mediated by generation of reactive oxygen species. These findings revealed that CMPP has a selective antitumor activity against cancer cells and warrants further clinical evaluation