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The use of adjunct chemical substances in the early postoperative period of periodontal surgical procedures is recommended due to the potential risk of trauma in the operated area. Chlorhexidine digluconate mouthwash is widely used but can cause adverse effects. Phthalocyanine derivatives are being studied as an alternative, demonstrating good antimicrobial activity, especially in the self-activated form, which does not require additional light or chemicals.

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Bone remodeling, a continuous process of resorption and formation, is essential for maintaining skeletal integrity and mineral balance. However, in cases of critical bone defects where the natural bone remodeling capacity is insufficient, medical intervention is necessary. Traditional bone grafts have limitations such as donor site morbidity and availability, driving the search for bioengineered scaffold alternatives.

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Objective: Immune checkpoint inhibitors (ICI) that block the programmed cell death 1 (PD-1) pathway have shown promise with limited benefit. We and others have shown in small patient cohorts that an early proliferative CD8 T-cell response in the blood may be predictive of clinical response. However, these studies lack detailed analyses and comparisons between monotherapy and combination therapies.

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Introduction: Chimeric antigen receptor (CAR) expressing T-cells have shown great promise for the future of cancer immunotherapy with the recent clinical successes achieved in treating different hematologic cancers. Despite these early successes, several challenges remain in the field that require to be solved for the therapy to be more efficacious. One such challenge is the lack of long-term persistence of CD28 based CAR T-cells in patients.

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Aim: With the aim of simultaneously modulating the epigenetic system and the protein kinase pathway, we selected the enzyme histone deacetylase (HDAC) and the Rho-associated protein kinases (ROCK) as desired targets to develop potential multitarget anticancer agents with additional antimetastatic properties. We report here the rational design, synthesis, and biological evaluation of the HDAC/ROCK multitarget inhibitors in pancreatic ductal adenocarcinoma (PDAC) and triple-negative breast cancer (TNBC).

Materials And Methods: A molecular docking study performed with the Gold software was used to develop HDAC/ROCK multitarget inhibitors.

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