Current Medicinal Chemistry - Online First

The present review was undertaken to clarify the potential role of the lysyl oxidase (Lox) family of enzymes in delaying graft dysfunction. Delayed graft failure is a well-known event that occurs post-transplantation period. Ischemia and trauma to the graft tissue before or during the operation procedures are likely to be the most important etiological causes of this complication. The lox proteins family including Lox and Lox- like proteins (LoxL1-4) are copper-dependent enzymes that catalyze the cross-linking of collagens to stabilize extracellular matrix (ECM). Hypoxia-induced factor 1-α (HIF-1α) and transforming growth factor β (TGF-β) are two upstream regulators of the Lox proteins family whose expression increased following hypoxia and tissue injury. Lox proteins’ overactivation upregulates several intracellular transduction pathways to promote oxidative stress (OS), ECM proteins accumulation, and epithelial to mesenchymal transition (EMT) contribute to vascular stiffness and tissue fibrogenesis, which increase the risk of graft failure post solid organ transplantation (SOT). Preclinical studies have shown that Lox protein inhibitors have the potential to prevent organ fibrosis. Regarding the molecular effects of Lox proteins in causing tissue fibrosis, these molecules can be further investigated as a drug target in reducing the possibility of organ fibrosis after allograft transplantation.

Mercury is a pervasive global pollutant, with primary anthropogenic sources including mining, industrial processes, and mercury-containing products such as dental amalgams. These sources release mercury into the environment, where it accumulates in ecosystems and enters the food chain, notably through bioamplification in marine life, posing a risk to human health. Dental amalgams, widely used for over a century, serve as a significant endogenous source of inorganic mercury. Studies have demonstrated that mercury vapor can be released from amalgams at room temperature due to material corrosion, potentially leading to chronic exposure. Pregnant women and children are particularly susceptible to mercury’s toxic effects, with research linking prenatal mercury exposure to developmental delays, neurocognitive deficits, and conditions such as autism spectrum disorder. Moreover, the long-term accumulation of mercury in the body raises concerns about delayed health impacts in individuals exposed during childhood. Recent findings suggest even low levels of mercury exposure may contribute to kidney damage mediated by oxidative stress, highlighting the importance of monitoring mercury levels in vulnerable populations. Prenatal mercury transfer and postnatal exposure through breastfeeding further amplify the risks. This review critically assesses the health implications of mercury exposure from dental amalgams, focusing on its impact on pregnancy and childhood development. It underscores the need for updated regulatory measures to mitigate mercury-related risks and calls for further research to clarify the extent of mercury’s long-term effects on human health.

The investigation of naturally derived anticancer drugs has gained prominence in cancer therapy research. Within a broad context, this review seeks to elucidate the molecular foundations and diverse mechanisms underlying these compounds to understand their pivotal role in advancing effective interventions. Additionally by employing a systematic approach, this study examined the interplay between cellular components, signaling pathways, and genetic factors, providing valuable insights into the regulatory networks governing the efficacy of these drugs. Categorization based on sources (plants, animals, marine organisms, and microbes) revealed unique bioactive constituents and therapeutic potential. Mechanistic investigations have revealed the ability of these compounds to induce apoptosis, inhibit angiogenesis, modulate metabolic processes, stimulate the immune system, and arrest the cell cycle. This overview encompasses both approved drugs and those undergoing clinical trials, highlighting their heightened efficacy and reduced toxicity compared to their synthetic counterparts. However, challenges persist in terms of standardization, quality control, and large-scale production. In conclusion, this review examined the potential of naturally derived anticancer drugs to contribute to advancements in cancer treatment and enhance patient outcomes. In addition to their effectiveness, natural anticancer drugs are generally less toxic and have fewer harmful side effects than conventional chemotherapies. This emphasizes the need for continued research, collaborative efforts, and addressing the regulatory and intellectual property challenges associated with natural products. This review provides a balanced perspective on the mechanisms, advantages, and prospects.

Large-scale infectious diseases have become a significant threat to human health and safety. The successful invention of vaccines is the most powerful means for preventing infectious diseases and has greatly improved global human health. Even during the pandemic of COVID-19, which has affected the world, vaccines have played an irreplaceable role. Microneedles (MNs) punctured the stratum corneum and formed microchannels in the skin allowing the vaccine to be efficiently recognized by the abundant antigen-presenting cells (APCs) in the skin to form specific immunity. Compared with traditional vaccination methods, MN transdermal immunization has the advantages of painlessness, easy storage, and efficient immune response. In this review, we summarize the types of vaccines, types of MNs, research progress and clinical research status of MN-based vaccines. We also cover various technologies for vaccine encapsulation, stable delivery of MN vaccines, and a wide range of potential clinical applications. We also outline the future development prospects of the MN system onboard to achieve better clinical benefits.

Curcumin is a natural plant pigment that has been widely used in food production, drug development, and textile engineering. Gaining a deep understanding of the biological activities of curcumin and obtaining high-purity curcumin are of vital importance for basic research and applications of curcumin. In this review, we summarize recent advances in curcumin, mainly focusing on the methods of extracting and purifying curcumin from turmeric as well as applications based on biological activity. We systematically describe the advantages and disadvantages of traditional and modern extraction technologies. The usual purification methods include conventional methods (such as macroporous resin column chromatography and silica gel column chromatography, etc.) and auxiliary modern technologies (such as high-speed countercurrent chromatography and supercritical fluid chromatography). In terms of biological activity, the phenolic hydroxy group and methoxy group of curcumin are closely related to its antioxidant activity, endowing it with strong antibacterial, anti-inflammatory, and antitumor properties. Moreover, the development direction based on its multiple biological activities is also discussed.

Plumbagin (PL) is an important natural active ingredient in traditional Chinese medicine derived from the Plumbago zeylanica L. It possesses a variety of biological activities, such as anti-inflammatory, anticancer, antioxidant, antimicrobial, and neuroprotective properties, and has great potential for utilization in disease treatment and prevention. Cancer and neurological and psychiatric diseases are two major categories of diseases that currently threaten the physical and mental health of human beings, and their increasing incidence is causing a serious economic burden to all humanity. Based on the physical and chemical properties and pharmacokinetics of plumbagin, this study will focus on summarizing the application research status of plumbagin in cancer, neurological, and psychiatric diseases and analyze the molecular targets and action pathways of its therapeutic efficacy. This study will also briefly summarize the application of plumbagin in other diseases, as well as the existing problems and future development direction of plumbagin in clinical application, aiming to provide new perspectives and strategies for the development of new drugs and the treatment of existing diseases.

Cervical cancer remains a significant global health concern, making it essential to investigate new treatment options continuously. This page provides an overview of the latest advancements and best practices in detection and intervention, including Pap smears, colposcopy, biopsy, immunotherapy, targeted therapies, chemotherapy, radiation therapy, and surgery. Surgical techniques such as radical hysterectomy and minimally invasive procedures have advanced to enhance patient outcomes and quality of life. Simultaneously, radiation therapy methods have been refined to maximize tumour control while reducing adverse effects. Chemotherapy remains vital, with new drugs and combination regimens demonstrating improved tolerance and efficacy. Immunotherapy, notably immune checkpoint inhibitors, has shown promise in advanced stages of cervical cancer. Additionally, targeted therapies that focus on specific biochemical pathways offer the potential for personalized treatment approaches. This review critically assesses ongoing research, evaluates existing data, and emphasizes the opportunities and challenges of each therapeutic approach. Ultimately, integrating these diverse treatment strategies is the key to enhancing patient outcomes.