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Kemp Schack posted an update 6 months ago
Zika virus (ZIKV) is an emerging arthropod-borne flavivirus that, upon infection, results in teratogenic effects and neurological disorders. ZIKV infections pose serious global public health concerns, prompting scientists to increase research on antivirals and vaccines against the virus. These efforts are still ongoing as the pathogenesis and immune evasion mechanisms of ZIKV have not yet been fully elaborated. Currently, no specific vaccines or drugs have been approved for ZIKV; however, some are undergoing clinical trials. selleck inhibitor Notably, several strategies have been used to develop antivirals, including drugs that target viral and host proteins. Additionally, drug repurposing is preferred since it is less costly and takes less time than other strategies because the drugs used have already been approved for human use. Likewise, different platforms have been evaluated for the design of vaccines, including DNA, mRNA, peptide, protein, viral vectors, virus-like particles (VLPSs), inactivated-virus, and live-attenuated virus vaccines. These vaccines have been shown to induce specific humoral and cellular immune responses and reduce viremia and viral RNA both in vitro and in vivo. Importantly, most of these vaccines have entered clinical trials. Understanding the viral disease mechanism will provide better strategies for developing therapeutic agents against ZIKV. This review provides a comprehensive summary of the viral pathogenesis of ZIKV and current advancements in the development of vaccines and drugs against this virus.Medullary thyroid carcinomas (MTC) are rare neoplasms derived from calcitonin-secreting cells of the thyroid. They can occur sporadically or as part of the multiple endocrine neoplasia type 2 syndromes. Overall, successful management of MTC patients heavily relies on the patient’s conditions, tumor stage, genetic background, and the medical team’s experience. Over the past 10 years, many consensus or near consensus of expert panels have been published for the treatment and follow-up of MTC (e.g., American Thyroid Association 2009, ATA 2015, European Society of Medical Oncology 2019, European Association of Nuclear Medicine 2020). The recent 2020 EANM guidelines recommend in particular to carry out 18F-FDOPA (6-18F-fluoro-L-3,4-dihydroxyphenylalanine) positron emission tomography/computed tomography scan (PET/CT scan) in MTC patients with persistent disease; however, this recommendation was not made in the 2015 ATA revised version. 18F-flurodeoxy glucose PET/CT scan is limited to aggressive forms, and PET imaging using 68Ga-somatostatin analogs appears suboptimal. This special article focuses on the clinical value of PET imaging in three common clinical scenarios (before initial thyroidectomy, before cervical reoperations for persistent/recurrent disease, and in the follow-up of metastatic cases).Agricultural workers experience higher rates of injury and illness than other occupational groups. NIOSH-supported agricultural centers in the U.S. are funded to reduce injury and illness but require effective partnerships with other agricultural organizations to achieve this goal. Our purpose was to understand the structure of agricultural organization connections within six states in the western U.S., including how different types of organizations connect to one another, and specifically where the High Plains Intermountain Center for Agricultural Health and Safety (HICAHS) is positioned in the agricultural organization network. An electronic survey was distributed to contacts within organizations that had a previous history with HICAHS leadership and advisory board members. The survey asked respondents about their position in the organization, years with the organization and frequency of contact in the past year. A social network analysis was undertaken to assess the connections between agricultural organizations using measures of centrality (density, closeness, betweenness), cliques, clusters, and brokers. A two-tier structure was identified with a core group of 21 organizations and a peripheral group of 30 organizations. Influence was centered in the core group as evidenced by high centrality scores with minimal bridging between organizations. HICAHS was on the periphery, but on the cusp of being in the core. Agricultural producers, agricultural extension and insurance companies were central in the network. Centers are in a unique position to promote collaboration with stakeholders. The social network analysis identified missing connections that need further development in order to address agricultural safety and health.
Phospholipase D1 (PLD1) is an enzyme of the phospholipase D (PLD) superfamily. It is involved in the occurrence of various tumors. However, its role in multiple myeloma (MM) remained undefined. This study aimed to investigate the mechanism of PLD1 in the therapy of myeloma disease.
Cell lines U266 and H929 were treated with PLD1 specific inhibitor VU0359595 combined bortezomib, a proteasome inhibitor. Their effects on MM cell proliferation, apoptosis, and relevant signal pathways of apoptosis were determined by cell counting kit-8 (CCK-8), real-time polymerase reaction chain (RT-PCR), ATP assay, and western blot.
PLD1 was highly expressed in U266 and H929 cells. VU0359595 didn’t affect the proliferation and apoptosis of MM cells. However, VU0359595 could enhance growth inhibition, decreasing mitochondrial membrane potentials (MMPs) and ATP levels of bortezomib treated MM cells. VU0359595 also strengthened bortezomib-induced apoptosis via activating caspase-8, caspase-9, caspase-3; and down-regulating the expressions of anti-apoptosis proteins BCL-2. In addition, the bortezomib-induced cytotoxicity on MM cells was significantly augmented by VU0359595 through efficient suppression of the mTOR/NF-κB signal pathway.
PLD1 inhibition can remarkably exert antitumor effects with bortezomib on MM, which is a novel potentially targeting therapeutic agent, especially for drug-resistant MM patients.
PLD1 inhibition can remarkably exert antitumor effects with bortezomib on MM, which is a novel potentially targeting therapeutic agent, especially for drug-resistant MM patients.
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