Erectile responses in reproduction have not been analyzed extensively because of the limitation of their visualization analyses of inner penile structure and its dynamic changes. In addition, the complex and rapid changes of erectile responses require new manipulation techniques suitable to regulate erected and flaccid status. The current review describes novel strategies for the above visualization of erection and regulation of the erectile responses.

Cancer-associated thrombosis is the second leading cause of death in patients with cancer. The highly metastatic triple-negative mouse breast cancer cell line 4T1 induces thrombus formation that is dependent on neutrophil extracellular traps (NETs) in transplanted mice when exposed to certain stimuli, such as lipopolysaccharide (LPS) injection. These findings suggest that 4T1 transplantation into mice increases the susceptibility to NET release, followed by thrombus formation in response to external stimuli. However, the blood levels of coagulation-associated factors in 4T1-bearing mice that are in a primed state without any stimulation remain unknown. In this study, we analyzed coagulation and fibrinolytic factors in the plasma of mice orthotopically transplanted with 4T1 cells. In 4T1-bearing mice, a NET marker, citrullinated histone H3, was detected in the tumor tissues and lungs, but not in the plasma. The presence of fibrin(ogen)-containing Ly6G-positive cell clusters in the lung vasculature suggested that NET release and NET-induced microthrombus formation occurred in the lungs. In plasma, increased levels of tissue factor and active and total plasminogen activator inhibitor-1 (PAI-1) suggested enhanced procoagulant activity and suppressed fibrinolysis. However, plasma thrombin–antithrombin complex levels, which reflect overt thrombin activation that forms fibrin clots, were similar in 4T1-bearing and non-transplanted mice. These findings indicate that 4T1 cell growth and metastasis in mice establish a pre-thrombotic state characterized by NET release and procoagulant potential, which requires a secondary trigger, such as LPS, to develop into pathological thrombosis. Therefore, 4T1-bearing mice may be useful as an in vivo model for exploring secondary triggers of pathological thrombosis.

The pharmacokinetics of drugs significantly affects their efficacy and adverse effects. Clarifying and predicting individual pharmacokinetic differences is crucial for the appropriate use of pharmaceuticals. Recent studies have suggested that the metabolic potential of intestinal bacteria may influence individual differences in pharmacokinetics. The consumption of probiotics, including supplements and fermented foods, has increased as a recent health trend. However, probiotics may also influence drug pharmacokinetics. In this study, we focused on the immunosuppressive drugs tacrolimus, everolimus, and cyclosporin A, which require careful dosing regimens, and investigated their interactions with microorganisms present in probiotics. Among the evaluated microorganisms, Bacillus subtilis exhibited a particularly strong drug degradation activity, with B. subtilis TO-A reducing the residual rates of tacrolimus and everolimus by 8 and 17%, respectively, in vitro. In a nonclinical pharmacokinetic trial, mice administered B. subtilis TO-A showed a significant reduction in the maximum blood concentration of tacrolimus. The concentration was 86.36 ± 63.61 ng/mL, much lower than that (212.8 ± 67.40 ng/mL) observed in the non-administered group. Based on these results, we can infer that orally ingested microorganisms can metabolize pharmaceuticals before reaching the small intestine, which is the primary site of absorption. These findings strongly suggest the need for caution when concurrently administering tacrolimus and probiotics in humans.

In Japan, education on preventing exposure to anticancer drugs should be conducted for outpatients receiving chemotherapy, based on the “Guideline for Preventing Occupational Exposure in Cancer Chemotherapy Drugs, 2019 Edition (guidelines 2019).” However, the educational content at each facility remains unclear. This study aimed to investigate the educational system and content in 461 cancer hospitals nationwide. We conducted a cross-sectional survey using a web questionnaire consisting of 27 questions covering four categories (background, patient educational system, content of patient education handouts, and issues in exposure prevention education). In total, 310 (67.2%) facilities responded, and 306 facilities were surveyed. Among the facilities surveyed, 96.7% (296/306 facilities) provided protection against exposure to injectable anticancer drugs, whereas only 33.4% (99/296 facilities) provided protection against exposure to oral anticancer drugs. Moreover, we analyzed the references and contents of the handouts used at the facilities. A total of 85% (209/244 facilities) of the facilities were creating handouts based on the 2019 guidelines. Approximately 85% of the facilities included “preventing exposure for body fluids and excretions” and “recommended preventing exposure period” in their handouts, but <60% included “handling of injectable agents” and “handling of oral anticancer agents.” Furthermore, in the free description section on issues in education, 27 responses mentioned “insufficient of evidence,” which was thought to be related to differences in educational content between facilities. In conclusion, it is necessary to establish a system for improving education to prevent exposure to oral anticancer drugs and standardize educational content through the creation of evidence.

The presence of treatment-resistant patients underscores the need for novel therapeutic options for affective and anxiety disorders. Kamikihito (KKT), a traditional kampo medicine used to treat mental anxiety and neurosis, has recently attracted attention because of its unique mechanism of action as an oxytocin-activating drug. However, the underlying mechanism remains unclear. In particular, for the optimal use of KKT in clinical practice, clarifying whether KKT affects the monoaminergic system, which is the primary target of first-line antidepressants for these disorders, is essential. By evaluating monoaminergic transporter activity in vitro, we found that KKT inhibited the noradrenaline transporter (NAT). In addition, in the tail suspension test, KKT shortened the duration of immobility posture, indicative of behavioral despair, in lipopolysaccharide-injected mice, similar to desipramine, a NAT inhibitor. Furthermore, a reduction in the immobility time following KKT administration was not observed in mice pretreated with N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4), a noradrenergic neurotoxin, indicating that the antidepressant-like effect of KKT is mediated through the noradrenergic system. To identify the ingredients of KKT that are transferred into the blood and brain, we analyzed the blood and brain tissues of mice after KKT administration using mass spectrometry. Geniposide and formononetin were identified and puerarin, gardoside, 3′,7-dihydroxy-4′-methoxyisoflavone 7-O-glucoside, and kazonol N were estimated as ingredients that distribute both in the blood and brain. Although these ingredients did not exhibit NAT inhibitory activity, the information presented in this pharmacokinetic study will be a valuable resource for future studies on the molecular mechanisms of KKT action.