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Endometriosis is one of the most common benign gynecological disorders in reproductive-aged women. The major symptoms are chronic pelvic pain and infertility. Despite its profound impact on women's health and quality of life, its pathogenesis has not been fully elucidated, it cannot be cured and the long-term use of drugs yields severe side effects and hinders fertility. This review aims to present the advances in pathogenesis and the newly reported lead compounds and drugsmanaging endometriosis. This paper investigated Genetic changes, estrogendependent inflammation induction, progesterone resistance, imbalance in proliferation and apoptosis, angiogenesis, lymphangiogenesis and neurogenesis, and tissue remodeling in its pathogenesis; and explored the pharmacological mechanisms, constitutive relationships, and application prospects of each compound in the text. To date, Resveratrol, Bay1316957, and bardoxifene were effective against lesions and pain in controlled animal studies. In clinical trials, Quinagolide showed no statistical difference with the placebo group; the results of phase II clinical trial of the IL-33 antibody have not been announced yet; clinical trial stage III of vilaprisan was suspended due to drug toxicity. Elagolix was approved for the treatment of endometriosis-related pain, but clinical studies of Elagolix for the pretreatment of patients with endometriosis to before In vitro fertilization treatment have not been fulfilled. The results of a clinical study of Linzagolix in patients with moderate to severe endometriosis-related pain have not been disclosed yet. Letrozole improved the fertility of patients with mild endometriosis. For endometriosis patients with infertility, oral GnRH antagonists and aromatase inhibitors are promising drugs, especially Elagolix and Letrozole. [ABSTRACT FROM AUTHOR]

A successful candidate for oral drug delivery needs to possess adequate solubility and dissolution rate to elicit its therapeutic action. Extensive research is being carried out to enhance the solubility of poorly soluble drugs through a number of techniques involving polymeric and non-polymeric approaches. Non-polymeric approaches such as micronization and nanocrystals are successful in improving the apparent solubility of drugs, but the sustenance of solubility is not always possible. Amorphous solid dispersions (ASDs) lead to solubility enhancement as well as the maintenance of solubility with the assistance of polymers, thereby improving bioavailability. Spray drying, hot melt extrusion (HME), and KinetiSol® technologies are some of the techniques capable of manufacturing ASDs. Each of these techniques has its own advantages and disadvantages in terms of processing challenges and applicability in preparing ASDs. The latter two technologies are similar in being fusion and non-solvent techniques to improve solubility. This review compares both HME and KinetiSol® techniques regarding mechanism, equipment design, formulation, and process parameters involved and scalability. [ABSTRACT FROM AUTHOR]

Escherichia coli topoisomerase I (EctopoI), a type IA DNA topoisomerase, relaxes the negative DNA supercoiling generated by RNA polymerase ( RNAP) during transcription elongation. Due to the lack of structural information on the complex, the exact nature of the RNAP-EctopoI interactions remains unresolved. Herein, we report for the first time, the structure-based modeling of the RNAP-EctopoI interactions using computational methods. Our results predict that the salt bridge as well as hydrogen bond interactions are responsible for the formation and stabilization of the RNAP-EctopoI complex. Our investigations provide molecular insights for understanding how EctopoI interacts with RNAP, a critical step for preventing hypernegative DNA supercoiling during transcription. [ABSTRACT FROM AUTHOR]