Notes

Implementing a crèche-based neighborhood sinking program within outlying Bangladesh: an operation evaluation.
The nucleotides were discovered in the early 19th century and a few years later, the role of such molecules in energy metabolism and cell survival was postulated. In 1972, a pioneer work by Burnstock and colleagues suggested that ATP could also work as a neurotransmitter, which was known as the "purinergic hypothesis". The idea of ATP working as a signaling molecule faced initial resistance until the discovery of the receptors for ATP and other nucleotides, called purinergic receptors. Among the purinergic receptors, the P2Y family is of great importance because it comprises of G proteincoupled receptors (GPCRs). GPCRs are widespread among different organisms. These receptors work in the cells' ability to sense the external environment, which involves to sense a dangerous situation or detect a pheromone through smell; the taste of food that should not be eaten; response to hormones that alter metabolism according to the body's need; or even transform light into an electrical stimulus to generate vision. Advances in understanding the mechanism of action of GPCRs shed light on increasingly promising treatments for diseases that have hitherto remained incurable, or the possibility of abolishing side effects from therapies widely used today.Central nervous system (CNS) cancers are among the most common and treatment-resistant diseases. The main reason for the low treatment efficiency of the disorders is the barriers against targeted delivery of anticancer agents to the site of interest, including the blood-brain barrier (BBB) and blood-brain tumor barrier (BBTB). BBB is a strong biological barrier separating circulating blood from brain extracellular fluid that selectively and actively prevents cytotoxic agents and majority of anticancer drugs from entering the brain. BBB and BBTB are the major impediments against targeted drug delivery into CNS tumors. Nanotechnology and its allied modalities offer interesting and effective delivery strategies to transport drugs across BBB to reach brain tissue. Integrating anticancer drugs into different nanocarriers improves the delivery performance of the resultant compounds across BBB. compound library inhibitor Surface engineering of nanovehicles using specific ligands, antibodies and proteins enhances the BBB crossing efficacy as well as selective and specific targeting to the target cancerous tissues in CNS tumors. Multifunctional nanoparticles (NPs) have brought revolutionary advances in targeted drug delivery to brain tumors. This study reviews the main anatomical, physiological and biological features of BBB and BBTB in drug delivery and the recent advances in targeting strategies in NPs-based drug delivery for CNS tumors. Moreover, we discuss advances in using specific ligands, antibodies, and surface proteins for designing and engineering of nanocarriers for targeted delivery of anticancer drugs to CNS tumors. Finally, the current clinical applications and the perspectives in the targeted delivery of therapeutic molecules and genes to CNS tumors are discussed.Transdermal drug delivery helps to circumvent the first-pass effect of drugs and to avoid drug-induced gastrointestinal tract irritation, compared with oral administration. With the extensive application of ethosomes in transdermal delivery, the shortages of them have been noticed continuously. Due to the high concentration of volatile ethanol in ethosomes, there are problems of drug leakage, system instability, and ethosome-induced skin irritation. Thus, there is a growing interest in the development of new generations of ethosomal systems. Functionalized ethosomes have the advantages of increased stability, improved transdermal performances, an extended prolonged drug release profile and site-specific delivery, due to their functional materials. To understand comprehensively understand this novel carrier, this review summarizes the properties of functionalized ethosomes, their mechanism through the skin and their modifications with different materials, validating their potential as promising transdermal drug delivery carriers. Although functionalized ethosomes have presented a greater role for enhanced topical delivery, challenges regarding their design and future perspectives are also discussed.
High-grade serous ovarian carcinoma (HGSOC) is one of the most common ovarian epithelial carcinomas. It is highly invasive, easily recurs after systemic treatment, and has a poor prognosis. Despite many new chemotherapeutic drugs and trials of combinations of different regimens that have been used in treatment attempts, there has been no meaningful progress in the treatment of HGSOC. With the development of gene sequencing technology, gene therapy has become a new direction for tumors treatment. It is reported that the P53 has a very high mutation rate in HGSOC, which provides a theoretical basis for the application of gene therapy in HGSOC patients. Recombinant human p53 adenovirus injection (rAd-p53) is the world's first approved oncology gene therapy drug.

In this article, we retrospectively analyzed 4 cases of HGSOC patients treated with rAdp53. Three of them were recurrent ovarian cancer, and one was the initial treatment. The treatment method was to apply recombinant human p53 adenovirus injection (ancer, promote the further development and progress of gene therapy in this field.
Through the remarkable efficacy of these 4 cases, we can see that the application of rAdp53 combined with chemotherapy can effectively control tumor lesions, prolong the survival time of patients, improve the quality of life of patients, which provide valuable experiences for rAd-p53 treatment in ovarian cancer, promote the further development and progress of gene therapy in this field.Marine sponge-associated fungi are promising sources of structurally interesting and bioactive secondary metabolites. Great plenty of natural products have been discovered from spongeassociated fungi in recent years. Here reviewed are 571 new compounds isolated from marine fungi associated with sponges in 2010-2018. These molecules comprised eight different structural classes, including alkaloids, polyketides, terpenoids, meroterpenoids, etc. Moreover, most of these compounds demonstrated profoundly biological activities, such as antimicrobial, antiviral, cytotoxic, etc. This review systematically summarized the structural diversity, biological function, and future potential of these novel bioactive natural products for drug discovery.
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