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Abstract Background Hypertension is the most frequently occurring adverse event of lenvatinib, recognized relatively early in its course. However, the trend in blood pressure after the initiation of lenvatinib and the outcomes with antihypertensive treatment are unclear. This study aimed to clarify the association between baseline blood pressure and the incidence of lenvatinib‐induced hypertension in patients with thyroid cancer. Methods This retrospective study included 65 patients without hypertension at the time of lenvatinib initiation. Patients were divided into two groups: those who developed hypertension grade ≥3 (HTN group) and those who did not develop hypertension grade ≥3 (non‐HTN group). Results Of the 65 patients, 46 (71%) developed hypertension grade ≥3. In both HTN and non‐HTN groups, blood pressure significantly increased the day after lenvatinib initiation. There was no significant difference in the elevated values of both the changes in systolic blood pressure (ΔSBP) and diastolic blood pressure (ΔDBP) between the two groups, with an average increase of 20 mmHg in SBP and 13 mmHg in DBP from baseline. The median (range) time to the onset of hypertension grade ≥3 was 2 days (1–12 days). In the multivariable analysis, patients with normal (SBP 120–129 mmHg and/or DBP 80–84 mmHg) or high‐normal baseline blood pressure (SBP 130–139 mmHg and/or DBP 85–89 mmHg) were at higher risk of developing hypertension grade ≥3 than those with optimal baseline blood pressure (SBP

Abstract Objective Placental extract, which contains various bioactive compounds, has been used as traditional medicine. Many studies have demonstrated additional applications of placental extract and provided a scientific basis for the broad spectrum of its effects. We have previously reported that porcine placental extract (PPE) strongly suppresses adipogenesis in a 3T3-L1 preadipocyte cell line, inhibiting differentiation. This study aimed to examine the effect of PPE on the accumulation of lipid droplets (LD) in adipose-derived mesenchymal stromal/stem cells (ASC). Results The study findings revealed that PPE decreased the size of LD during the differentiation of ASC into mature adipocytes. RT-qPCR analysis revealed that PPE increased the gene expression of lysosomal acid lipase A (Lipa), a lipolysis-related gene, in ASC-differentiated adipocytes. However, no differences were noted in the adipocyte differentiation markers (Pparg, Cebpa, and Adipoq), or the adipogenesis-related genes (Dgat1, Dgat2, Fasn, Soat1, and Soat2). In addition, PPE promoted autophagosome formation, which was partially co-localized with the LD, indicating that PPE accelerated the degradation of LD by inducing autophagy (termed lipophagy) during the differentiation of ASC into mature adipocytes. These results suggest that the use of PPE may be a potential novel treatment for regulating adipogenesis for the treatment of obesity.

Antimicrobial photodynamic therapy (aPDT) used to sterilize carious dentin may irritate pulp tissues because of tissue-penetrating laser and singlet oxygen generation. This study aimed to assess the effects of aPDT on rat pulp tissues. A cavity formed in a rat maxillary first molar was treated with aPDT. The combined photosensitizer and laser irradiation conditions in the aPDT groups were as follows: methylene blue and 100 mW for 60 s, brilliant blue (BB) and 100 mW for 60 s, BB and 50 mW for 120 s, and BB and 200 mW for 30 s. Each cavity was treated with an all-in-one adhesive and filled with flowable resin. aPDT was not applied for the control. In each group, the rats were sacrificed on postoperative days 1 and 14, and thin sections of the treated teeth were prepared. Pulp tissue disorganization (PTD), inflammatory cell infiltration (ICI), and tertiary dentin formation (TDF) were evaluated. At 1-day evaluation, there were significant differences between the aPDT group and controls with respect to PTD and ICI (p < 0.01); 14 days later, almost all specimens showed tertiary dentin formation. The application of aPDT caused reversible damage to the rat pulp, while in the long term, healing occurred with the formation of tertiary dentin.

BackgroundProteinuria is the most frequent adverse event of lenvatinib use. However, the association between lenvatinib-induced proteinuria and renal dysfunction remains unclear.MethodsWe retrospectively reviewed medical records of patients with thyroid cancer without proteinuria treated with lenvatinib as a first-line systemic therapy at the initiation of treatment to assess the association between lenvatinib-induced proteinuria and renal function and the risk factors for the development of ≥3+ proteinuria on a dipstick test. Proteinuria was assessed by the dipstick test throughout the treatment in all cases.ResultsOf the 76 patients, 39 developed ≤2+ proteinuria (low proteinuria group) and 37 developed ≥3+ proteinuria (high proteinuria group). There was no significant difference in estimated glomerular filtration rate (eGFR) between high and low proteinuria groups at each time point, but there was a trend toward a significant decrease in eGFR of -9.3 ml/min/1.73 m2 in all patients after 2 years of treatment. The percentage of change in eGFR (ΔeGFR) significantly decreased in the high proteinuria group compared to that in the low proteinuria group (ΔeGFR: -6.8% vs. -17.2%, p=0.04). However, there was no significant difference in development of severe renal dysfunction with eGFR

Abstract The relationships between posture and perception have already been investigated in several studies. However, it is still unclear how perceptual bias and experiential contexts of human perception affect observers’ perception when posture is changed. In this study, we hypothesized that a change in the perceptual probability caused by perceptual bias also depends on posture. In order to verify this hypothesis, we used the Necker cube with two types of appearance, from above and below, although the input is constant, and investigated the change of the probability of perceptual content. Specifically, we asked observers their perception of the appearance of the Necker cube placed at any of the five angles in the space of virtual reality. There were two patterns of neck movement, vertical and horizontal. During the experiment, pupil diameter, one of the cognitive indices, was also measured. Results showed that during the condition of looking down vertically, the probability of the viewing-from-above perception of the Necker cube was significantly greater than during the condition of looking up. Interestingly, the pupillary results were also consistent with the probability of the perception. These results indicate that perception was modulated by the posture of the neck and suggest that neck posture is incorporated into ecological constraints.

Abstract Background Elastomeric pumps (EPs) are devices that allow quantitative and continuous drug administration without the need for electronic control, and they are used by being filled with anticancer agents. Although the package inserts of several manufacturers that provide EPs describe the relationship between the flow rate per unit time and temperature, the solution is only saline solution or 5% glucose solution, and data on anticancer drugs have not been published. In this study, we focused on 5-fluorouracil (5-FU), a drug frequently used in cancer chemotherapy, and examined the effect of changes in standard of EPs and temperature on drug emission. Methods We evaluated the EP data of patients treated with Baxter Infusor® LV5 and SV2.5 in terms of emission rate, relationship between 5-FU prescription amount and emission rate, and relationship between emission rate and monthly air temperature in LV5 and SV2.5. The number of EPs sampled in the study was N = 5708 (n = 2988 for LV5 and n = 2720 for SV2.5). Results In LV5, the emission rate varied from 88 to 97% (median 94.0%), whereas in SV2.5, the emission rate was observed as 97 to 98% (median 97.4%). The 5-FU prescription amount and the emission rate were not correlated in LV5 and SV2.5, respectively (LV5; y = − 0.0015x + 97.305, R 2 = 0.0226, SV2.5; y = − 0.001x + 100.25, R 2 = 0.0466). LV5 showed a higher emission rate in the months with higher air temperature and a lower emission rate in the month with lower air temperature. In addition, LV5 showed a significant reduction in emission rate compared with SV2.5 in all months (P

Abstract Background Because cisplatin (CDDP) decreases upon light exposure, it is necessary to prevent such exposure during administration. However, the shielding conditions employed are not uniform. Therefore, in this study, we examined the shielding effects of four shading covers, which are commonly used to ensure the stability of CDDP in clinical settings. Methods Four shielding conditions, along with a control, were tested under a 1000-Lux white fluorescent lamp at room temperature: aluminum foil (Al), brown shading cover (BSC), yellow shading cover (YSC), milky-white anti-exposure cover (MAC), and no shading cover (NSC). Under each shielding condition, the relationship between the wavelength and transmittance was monitored in the range of 200–800 nm. CDDP was diluted to three concentration levels: 50, 100, and 250 μg/mL. Furthermore, the amount of remaining CDDP and the pH in the solutions were measured for 120 h. Results We found that BSC, YSC, and MAC conditions allowed various levels of transmittance; however, Al could not completely transmit light at all wavelengths. Moreover, we showed that the CDDP decreased under MAC and NSC conditions in a time-dependent manner, whereas this decrease was prevented under Al, BSC, and YSC conditions till 120 h. We also demonstrated increases in pH under MAC and NSC conditions in a time-dependent manner, which was prevented under Al, BSC, and YSC conditions till 120 h. Similar results were observed for all three CDDP concentration levels. The results also indicated the approximate relationship between the amount of remaining CDDP and the pH increase. Conclusions Considering the opacity of each cover, our results suggest that BSC and YSC are useful and effective for minimizing CDDP degradation in clinical settings. Our results also indicate the alternatives for preparing, storing, and administering CDDP in clinical facilities, making the treatment schedule more flexible. Cumulatively, these findings indicate that the use of the appropriate shading covers, such as BSC or YSC, prevents the decrease in CDDP under fluorescent lighting, potentially contributing to achieving its full therapeutic effect.

As time plays a fundamental role in our social activities, scholars have studied temporal perception since the earliest days of experimental psychology. Since the 1960s, the ubiquity of color has been driving research on the potential effects of the colors red and blue on temporal perception and on its underlying mechanism. However, the results have been inconsistent, which could be attributed to the difficulty of controlling physical properties such as hue and luminance within and between studies. Therefore, we conducted a two-interval duration-discrimination task to evaluate the perceived duration of color stimuli under different equiluminant conditions: subjective or pupillary light reflex (PLR)-based equiluminance. The results, based on psychometric functional analyses and simultaneous pupillary recordings, showed that the perceived duration of red was overestimated compared with blue even when the intensity of the stimulus was controlled based on subjective equiluminance (Experiment 1). However, since blue is known to induce a larger PLR than red despite equiluminance, we conducted a controlled study to distinguish the indirect effect of pupillary response to temporal perception. Interestingly, the effect observed in Experiment 1 faded when the luminance levels of the two stimuli were matched based on PLR response (Experiment 2). These results indicate that duration judgement can be affected not only by the hue but also by different equiluminance methods. Furthermore, this causality between the equiluminance method and temporal perception can be explained by the fluctuations in incident light entering the pupil.

Parkinson’s disease (PD) patients often complain of pain, but this problem has been neglected and is poorly understood. High mobility group box-1 (HMGB1), an alarmin/damage-associated molecular patterns protein, is increased in the cerebrospinal fluid in PD patients. However, little is known of the relationship between HMGB1 and pain associated with PD. Here, we investigated the role of central HMGB1 in the regulation of nociceptive hypersensitivity in a mouse model of PD. Male ddY mice were microinjected unilaterally with 6-hydroxydopamine (6OHDA) into the striatum. These hemi-PD mice were treated with anti-HMGB1 neutralizing antibody (nAb; 10 µg in 10 µL) by intranasal (i.n.) administration. The mechanical hypersensitivity of the hind paws was evaluated with the von Frey test. Spinal microglial activity was analyzed by immunostaining for ionized calcium-binding adapter molecule 1. The 6OHDA-administered mice displayed unilateral loss of dopamine neurons in the substantia nigra and mechanical hypersensitivity in both hind paws. Moreover, spinal microglia were activated in these hemi-PD mice. Twenty-eight days after the 6OHDA injections, repeated i.n., but not systemic, treatment with anti-HMGB1 nAb inhibited the bilateral mechanical hypersensitivity and spinal microglial activation. However, the anti-HMGB1 nAb did not ameliorate the dopamine neuron loss. Moreover, intracerebroventricular injection with recombinant HMGB1 induced mechanical hypersensitivity. These findings indicate that HMGB1 is involved in the maintenance of nociceptive symptoms in hemi-PD mice via spinal microglial activation. Therefore, central HMGB1 may have potential as a therapeutic target for pain associated with PD.

Abstract Background Adipogenesis, the process of preadipocyte differentiation to mature adipocytes accompanied by accumulation of intracytoplasmic lipid droplets, is regulated by various genetic and environmental factors, and closely associated with the development of obesity. Numerous recent studies suggest that some bioactive peptides and proteins derived from animals, and chemical compounds isolated from plants may be useful for prevention and treatment of obesity and obesity-related chronic diseases. In the present study, we examined the broad spectrum of effects of placental extract, with a focus on the influence of placental extract on adipogenesis. Method We cultured 3T3-L1 cells, which are widely used as a model of white preadipocytes, under differentiation conditions in the presence of porcine placental extract (PPE) for 8 days, and then stained the lipid droplets accumulated in the cytoplasm with Oil Red O. We also analyzed the effects of PPE on the mitogen-activated protein kinases (MAPKs) signaling, mitotic clonal expansion (MCE) and gene expressions associated with 3T3-L1 differentiation. Results When we cultured 3T3-L1 cells with PPE under differentiation conditions, the accumulation of lipid droplets and expression of adipocyte differentiation marker genes (Cebpa, Pparg, Slc2a4, Fasn and Adipoq) were dramatically attenuated. The suppressive activity of PPE against adipogenesis was heat-stable and recovered in a low-molecular-weight fraction after ultrafiltration (

Summary: Mammary ductal dysplasia is a phenotype observed in precancerous lesions and early-stage breast cancer. However, the mechanism of dysplasia formation remains elusive. Here we show, by establishing a novel dysplasia model system, that estrogen, a female hormone, has the potential to cause mammary ductal dysplasia. We injected estradiol (E2), the most active form of estrogen, daily into scid mice with a defect in non-homologous end joining repair and observed dysplasia formation with cell proliferation at day 30. The protooncogene Myc is a downstream target of estrogen signaling, and we found that its expression is augmented in mammary epithelial cells in this dysplasia model. Treatment with a Myc inhibitor reduced E2-induced dysplasia formation. Moreover, we found that isoflavones inhibited E2-induced dysplasia formation. Our dysplasia model system provides insights into the mechanistic understanding of breast tumorigenesis and the development of breast cancer prevention. : Molecular Biology; Cell Biology; Cancer Subject Areas: Molecular Biology, Cell Biology, Cancer