Deciphering Tuberculous Meningitis: From Clinical Challenges to Novel Models and Pathogenic Pathways.

IF 2.9 4区 医学 Q3 CHEMISTRY, MEDICINAL Current topics in medicinal chemistry Pub Date : 2024-01-29 DOI:10.2174/0115680266282277240122073451
Mohamad Mosa Mubarak, Shahnawaz Majeed, Hadiya Amin Kantroo, Zubair Ahmad Wani, Abbass Malik, Zahoor Ahmad, Ishfaq Ahmad Baba
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Abstract

During and after the COVID-19 pandemic,Tuberculosis (TB) has reestablished with higher figures due to interruptions in the Directly Observed Treatment Short course (DOTS) despite underreporting. The rising consequences would have extended to extra-pulmonary forms of TB as well, including Tuberculous Meningitis (TBM). Considering the fact that TBM is the most dangerous and worst form of TB, we found the need to scan the literature to highlight various aspects of TBM. Epidemiology of TBM is proportionally less frightening, but the consequent mortalities and morbidities are more alarming than pulmonary TB. Here, we address critical research gaps in Tuberculous Meningitis that warrant further investigations. The highlighted aspects encompass a comprehensive understanding of TBM's clinical presentation and improved diagnostic tools for timely detection, the exploration of innovative chemotherapies and surgical interventions, the unraveling of the role of the blood-brain barrier in disease onset, investigating of the contributions of various brain cells to TBM development, deciphering the complex inflammatory response, exploring the involvement of Matrix Metalloproteinases in tissue damage, delving into host-pathogen genetics influencing susceptibility, utilizing robust in-vivo and in-vitro models for mechanistic insights, and more importantly between TBM and SARS-COVID-19 are discussed. Addressing these gaps will substantially advance our understanding of TBM's complex pathogenesis, contributing to more effective diagnostic, therapeutic, and preventive strategies against this debilitating disease.

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解密结核性脑膜炎:从临床挑战到新型模型和致病途径。
在 COVID-19 大流行期间和之后,尽管报告不足,但由于短期直接观察治疗(DOTS)的中断,结核病(TB)的发病率再次上升。这种上升的后果还将扩展到肺外形式的结核病,包括结核性脑膜炎(TBM)。考虑到结核性脑膜炎是最危险、最严重的结核病,我们认为有必要对文献进行扫描,以突出结核性脑膜炎的各个方面。从比例上看,TBM 的流行病学并不那么可怕,但其造成的死亡率和发病率却比肺结核更令人担忧。在此,我们探讨了结核性脑膜炎方面值得进一步研究的关键研究空白。研究重点包括:全面了解结核性脑膜炎的临床表现,改进诊断工具以便及时发现;探索创新的化学疗法和外科干预措施;揭示血脑屏障在发病中的作用;研究各种脑细胞对结核性脑膜炎发展的贡献、讨论了复杂的炎症反应,探索基质金属蛋白酶在组织损伤中的参与,深入研究影响易感性的宿主-病原体遗传学,利用强大的体内和体外模型进行机理研究,以及更重要的 TBM 和 SARS-COVID-19 之间的关系。填补这些空白将极大地推动我们对 TBM 复杂发病机制的了解,有助于针对这种使人衰弱的疾病制定更有效的诊断、治疗和预防策略。
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来源期刊
CiteScore
6.40
自引率
2.90%
发文量
186
审稿时长
3-8 weeks
期刊介绍: Current Topics in Medicinal Chemistry is a forum for the review of areas of keen and topical interest to medicinal chemists and others in the allied disciplines. Each issue is solely devoted to a specific topic, containing six to nine reviews, which provide the reader a comprehensive survey of that area. A Guest Editor who is an expert in the topic under review, will assemble each issue. The scope of Current Topics in Medicinal Chemistry will cover all areas of medicinal chemistry, including current developments in rational drug design, synthetic chemistry, bioorganic chemistry, high-throughput screening, combinatorial chemistry, compound diversity measurements, drug absorption, drug distribution, metabolism, new and emerging drug targets, natural products, pharmacogenomics, and structure-activity relationships. Medicinal chemistry is a rapidly maturing discipline. The study of how structure and function are related is absolutely essential to understanding the molecular basis of life. Current Topics in Medicinal Chemistry aims to contribute to the growth of scientific knowledge and insight, and facilitate the discovery and development of new therapeutic agents to treat debilitating human disorders. The journal is essential for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important advances.
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