Heterocyclic compounds offer a high degree of structural diversity and have proven to be broadly and economically useful as therapeutic agents. Comprehensive research on diverse therapeutic ...potentials of heterocycles compounds has confirmed their immense significance in the pathophysiology of diseases. Heterocyclic pyrimidine nucleus, which is an essential base component of the genetic material of deoxyribonucleic acid, demonstrated various biological activities. The present review article aims to review the work reported on therapeutic potentials of pyrimidine scaffolds which are valuable for medical applications during new generation.
The explosive growth in Big Data has attracted much attention in designing efficient indexing and search methods recently. In many critical applications such as large-scale search and pattern ...matching, finding the nearest neighbors to a query is a fundamental research problem. However, the straightforward solution using exhaustive comparison is infeasible due to the prohibitive computational complexity and memory requirement. In response, approximate nearest neighbor (ANN) search based on hashing techniques has become popular due to its promising performance in both efficiency and accuracy. Prior randomized hashing methods, e.g., locality-sensitive hashing (LSH), explore data-independent hash functions with random projections or permutations. Although having elegant theoretic guarantees on the search quality in certain metric spaces, performance of randomized hashing has been shown insufficient in many real-world applications. As a remedy, new approaches incorporating data-driven learning methods in development of advanced hash functions have emerged. Such learning-to-hash methods exploit information such as data distributions or class labels when optimizing the hash codes or functions. Importantly, the learned hash codes are able to preserve the proximity of neighboring data in the original feature spaces in the hash code spaces. The goal of this paper is to provide readers with systematic understanding of insights, pros, and cons of the emerging techniques. We provide a comprehensive survey of the learning-to-hash framework and representative techniques of various types, including unsupervised, semisupervised, and supervised. In addition, we also summarize recent hashing approaches utilizing the deep learning models. Finally, we discuss the future direction and trends of research in this area.
Leadership skills in a public health professional (PHP) are more important today in view of rapidly changing disease pattern, higher priority to universal health coverage, health in all policies, ...health being demanded as a human right, and emergence of pandemics from zoonotic diseases. Most of us become accidental leaders as we never receive training in leadership skills. This not only undermines the effectiveness of PHP but also undermines the credibility of public health as a specialty. Jim Collin's five levels of leadership are useful to understand the various levels of leadership for a PHP. Technical excellence which denotes first level of leadership is necessary but not sufficient to become a leader. One needs team work, emotional competencies, prioritization ( first things first), listening skills, advocacy, negotiation, networking skills, along with conviction, commitment, and courage to do what one thinks is right. Leadership is a life-long journey, not a destination. Being engaged in leadership for more than a decade, I developed a three domain leadership capacity development model very useful in designing and conducting leadership development trainings to develop leadership skills among PHPs, academicians, and health researchers.
Adulteration in food has been a concern since the beginning of civilization, as it not only decreases the quality of food products but also results in a number of ill effects on health. Authentic ...testing of food and adulterant detection of various food products is required for value assessment and to assure consumer protection against fraudulent activities. Through this review we intend to compile different types of adulterations made in different food items, the health risks imposed by these adulterants and detection methods available for them. Concerns about food safety and regulation have ensured the development of various techniques like physical, biochemical/immunological and molecular techniques, for adulterant detection in food. Molecular methods are more preferable when it comes to detection of biological adulterants in food, although physical and biochemical techniques are preferable for detection of other adulterants in food.
Cancer is one of the most serious medical problem and second leading cause of death in the world, characterized by a deregulation of the cell cycle which mainly results in a progressive loss of ...cellular differentiation and uncontrolled cellular growth. The benzimidazole is a heterocyclic moiety found in extensive number of natural and biological active molecules. Benzimidazole derivatives might be considered as auxiliary isosters of nucleotides having attached heterocyclic cores in their structures, cooperate effortlessly with biopolymers and have potential action for chemotherapeutic applications. Benzimidazole and its derivatives displayed a wide range of biological activity because of its structural similarity with the naturally occurring nucleotides. Benzimidazole has established huge alertness in current time and is extremely significant heterocyclic pharmacophore in recent drug innovation and medicinal chemistry. The present review summarizes the chemistry of various substituted benzimidazole derivatives with their antiproliferative significance towards the various cancer cell lines such as HCT116, MCF7, HeLa, HepG2, A549 and A431.
Antimicrobial resistance (AMR) has emerged as a major threat to public health estimated to cause 10 million deaths annually by 2050. India carries one of the largest burdens of drug-resistant ...pathogens worldwide. NDM-1 reported in 2008, rapidly spread to other countries was named after India's capital. India is one of the largest consumers of antibiotics worldwide, and antibiotic sale is increasing rapidly. AMR develops when microbes develop mechanisms to evade the action of antimicrobials. The factors that contribute to AMR include irrational and overuse of antibiotics. In India, various actions have been taken including setting up of a National Task Force on AMR Containment (2010), "Chennai Declaration" by a consortium of the Indian Medical Societies (2012), Setting of Indian Council of Medical Research national surveillance network of laboratories, "Redline" campaign for educating public and National Action Plan on AMR 2017. There is a need integrating AMR education in medical education. India needs to start the subspecialty of infectious diseases and strengthen laboratory services. Every hospital needs to have an AMR policy including infection control, improvement in hygiene, and sanitation and antibiotic use. An element of research needs to be integrated into the AMR policy and encouragement of the pharmaceutical industry to develop "superbug antibiotics." Unless AMR is addressed effectively the gains made in health are likely to be lost.
Anti‐cancer therapies targeting and damaging the DNA have been extensively used in the last 50 years since the discovery of nitrogen mustards, antimetabolites and platin agents. The use of these ...drugs is often limited by dose‐limiting side effects related to their poor specificity. In recent years, much effort has been put on the discovery and development of compounds that would exploit defects in DNA repair in cancer cells such as Wee1, Chk1 or PARP1 inhibitors. However, not all cancers respond to these inhibitors. Recently, new developments towards specifically targeting broader characteristics of cancer such as replication stress (RS) and lost redox homeostasis have emerged. Oncogenes induce proliferation signals, which also result in replication‐associated DNA damage, i.e. RS. Our knowledge into overall causes of RS, lesions produced and how these are signalled in cells to activate cell cycle checkpoints is evolving. Inhibition of ATR, which would normally keep non‐deleterious levels of RS, induces intolerable RS levels for cancer cells. Interestingly, links between replication and transcription appear to underlie RS along with a reduction of the dNTP pool. Remarkably, sanitization of the dNTP pool by MutT homologue 1, impeding incorporation of oxidized dNTPs into the DNA, seems to be crucial for cancer cell survival. In this minireview we present an overview of current and novel strategies to target DNA repair and exploit DNA damage to treat cancer. We present the current models for cancer‐associated RS as well as cancer phenotypic lethality. Both strategies are poised to better target cancer cells and reduce side effects.
Emerging data demonstrate homologous recombination (HR) defects in castration-resistant prostate cancers, rendering these tumours sensitive to PARP inhibition. Here we demonstrate a direct ...requirement for the androgen receptor (AR) to maintain HR gene expression and HR activity in prostate cancer. We show that PARP-mediated repair pathways are upregulated in prostate cancer following androgen-deprivation therapy (ADT). Furthermore, upregulation of PARP activity is essential for the survival of prostate cancer cells and we demonstrate a synthetic lethality between ADT and PARP inhibition in vivo. Our data suggest that ADT can functionally impair HR prior to the development of castration resistance and that, this potentially could be exploited therapeutically using PARP inhibitors in combination with androgen-deprivation therapy upfront in advanced or high-risk prostate cancer.Tumours with homologous recombination (HR) defects become sensitive to PARPi. Here, the authors show that androgen receptor (AR) regulates HR and AR inhibition activates the PARP pathway in vivo, thus inhibition of both AR and PARP is required for effective treatment of high risk prostate cancer.
Background
Cancer is at present one of the leading causes of death in the world. It accounts for 13% of deaths occurred worldwide and is continuously rising, with an estimated million of deaths up to ...2030. Due to poor availability of prevention, diagnosis and treatment of breast cancer, the rate of mortality is at alarming level globally. In women, hormone-dependent estrogen receptor positive (ER+) breast cancer making up approximately 75% of all breast cancers. Hence, it has drawn the extensive attention of researchers towards the development of effective drugs for the treatment of hormone-dependent breast cancer. Estrogen, a female sex hormone has a vital role in the initiation and progression of breast malignancy. Therefore, estrogen receptor is the central target for the treatment of breast cancer.
Conclusion
In this review, we have studied various classes of antiestrogens that have been designed and synthesized with selective binding for estrogen alpha receptor (ER). Since estrogen receptor α is mainly responsible for the breast cancer initiation and progression, therefore there is need of promising strategies for the design and synthesis of new therapeutic ligands which selectively bind to estrogen alpha receptor and inhibit estrogen dependent proliferative activity.
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