Glioblastoma (GBM) is the most malignant form of glioma. Glioma stem cells (GSCs) contribute to the initiation, progression, and recurrence of GBM via their self-renewal potential and tumorigenicity. This review presents a brief overview of the influences of two protein posttranslational modifications in GSCs on the properties of GSCs and malignancy of GBM: (I) the ubiquitination of transforming growth factor (TGF)-β receptor (TGFBR) by SMAD-specific E3 ubiquitin protein ligase 2 (SMURF2) and (II) the phosphorylation of extracellular signal-regulated kinase 5 (ERK5) by mitogen-activated protein kinase/ERK kinase 5 (MEK5). The phosphorylation state of SMURF2Thr249 regulates the stemness and tumorigenicity of GSCs via the ubiquitin-dependent modification of the TGFBR-SMAD-SOX axis, along with the downregulation of SMURF2Thr249 phosphorylation in patients with GBM. MEK5 controls the self-renewal and tumorigenic potential of GSCs by phosphorylating the ERK5-signal transducer and activator of transcription 3 (STAT3) axis concomitant with high expression and activity of ERK5 in GSCs. These findings contributed to our understanding of the molecular mechanisms underlying the maintenance of the stemness and tumorigenicity of GSCs through protein posttranslational modifications. We propose that these two protein posttranslational modifications in GSCs might be explored as an effective therapeutic approach against various cancers whose malignancies are associated with the stemness of cancer stem cells.

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.

Exposure to ionizing radiation during early pregnancy poses serious risks to fetal development, particularly during organogenesis. In this study, we evaluated the protective effects of AHCC^®, a standardized extract of Lentinula edodes mycelia with known immunomodulatory and metabolic properties, using an ICR mouse model. Intraperitoneal administration of AHCC prior to 1.4-Gy γ-irradiation on gestational day 9 significantly reduced the incidence of tail malformations and diaphragmatic hernias, without affecting implantation or fetal survival. Additionally, lifelong AHCC ingestion across three generations did not alter reproductive parameters, namely, gestation length and litter size, supporting its safety during pregnancy. These findings suggest that AHCC may mitigate radiation-induced teratogenic effects through maternal immune modulation, without compromising reproductive outcomes.

Dai-kenchu-to is used to prevent and relieve ileus post-gastrectomy; however, it has been reported to cause hepatobiliary injury in 0.3% of patients, and knowledge regarding its risk in this context is limited. In this study, we aimed to evaluate the effect of dai-kenchu-to, a representative traditional Japanese herbal medicine, on the risk of hepatobiliary injury in patients with gastric cancer who underwent gastrectomy, using real-world data from acute care hospitals. The diagnosis procedure combination data of patients admitted with gastric cancer who underwent gastrectomy between April 2008 and May 2019 were analyzed. The collected data included sex, age, comorbid injuries and illnesses at admission, medication records during hospitalization, and tumor node metastasis classifications. The primary outcome, occurrence of hepatobiliary injury, was identified using records of the use of hepatoprotective agents or cholagogues. The odds ratios of dai-kenchu-to for predisposition to hepatobiliary injury after gastrectomy were estimated using multivariate logistic regression analysis. Herein, 33137 gastric cancer patients who underwent gastrectomy were included in the analysis. The incidences of hepatobiliary injury among patients in the dai-kenchu-to-exposed and non-exposed groups were both 5.9%. The multivariate odds ratio of dai-kenchu-to exposure for hepatobiliary injury was 0.97 (95% confidence interval, 0.73-1.29; p = 0.847). In this study, no risk of moderate-to-severe hepatobiliary injury due to the postoperative administration of dai-kenchu-to was noted in patients with gastric cancer who had undergone gastrectomy. These results provide information regarding the safety of dai-kenchu-to use after gastrectomy in patients with gastric cancer.

This study established experimental models of acute lung injury (ALI) both in vitro, using human alveolar epithelial cells, and in vivo, using murine models, with ALI induced by lipopolysaccharide (LPS). Propofol was administered to the animal models, and its effects on alveolar epithelial cell damage, lung tissue pathology, and inflammatory mediator levels were evaluated to assess its potential protective role against lung injury. The results showed that LPS-induced reactive oxygen species (ROS) played a central role in the development of ALI in both the cell and animal models, triggering pyroptosis of alveolar epithelial cells. This, in turn, led to the release of pro-inflammatory cytokines, exacerbating the lung injury. Importantly, propofol was found to reduce LPS-induced ALI by inhibiting ROS production and modulating key proteins involved in the pyroptosis pathway. These findings offer new insights into the mechanisms underlying ALI, providing a basis for the development of clinical treatments and suggesting promising therapeutic strategies for ALI patients.

Histone deacetylases (HDACs) regulate chromatin structure and gene expression, and their inhibition has been proposed as a radioprotective strategy. However, few studies have compared multiple HDAC inhibitors (HDACis) under identical conditions. This study evaluated the efficacy of seven HDACis in a mouse total body irradiation (TBI) model. Male ICR mice received 7.5 Gy TBI followed by a single administration of valproic acid (VPA; 300 or 600 mg/kg), sodium butyrate (NaB; 500 or 1000 mg/kg), trichostatin A (TSA; 0.5 or 1.0 mg/kg), vorinostat (10 or 50 mg/kg), panobinostat (25 or 50 mg/kg), givinostat (5 or 10 mg/kg), or entinostat (25 or 50 mg/kg). Survival was monitored for 20 d. Only VPA at 600 mg/kg significantly improved survival compared with vehicle (overall p = 0.00241; p = 0.0039 vs. vehicle), while all other HDACis showed no significant benefit. VPA's efficacy may reflect a combination of effects on DNA repair, inflammation, and redox regulation rather than HDAC inhibition alone. These findings suggest VPA to be a promising candidate for radioprotection and emphasize the need for further studies to optimize dosing and explore underlying mechanisms.

Neuroimaging in rodents holds promise for advancing our understanding of the central nervous system (CNS) mechanisms that underlie chronic pain. Employing two established, but pathophysiologically distinct rodent models of chronic pain, the aim of the present study was to characterize chronic pain-related functional changes with resting-state functional magnetic resonance imaging (fMRI). In Experiment 1, we report findings from Lewis rats 3 weeks after Complete Freund's adjuvant (CFA) injection into the knee joint (n = 16) compared with the controls (n = 14). In Experiment 2, Sprague-Dawley rats were scanned 2 weeks after partial sciatic nerve ligation (PSNL) (n = 25) or sham surgery (n = 19). CFA and PSNL induced typical behavioral patterns consistent with inflammatory and neuropathic pain, respectively. Functional magnetic resonance imaging analyses comprised (1) independent component analysis (ICA) decompositions, (2) assessment of graph measures, (3) seed-based functional connectivities, and (4) predictions of chronic pain based on supervised machine learning. In both models, we detected changes in default mode network (DMN) activity. Local and global graph measures were generally similar across groups. However, regardless of the pain model, we observed a significant reduction in the betweenness centrality hub disruption index (HDI) in chronic pain compared with the controls. Finally, employing supervised machine learning in combination with a deep learning approach, chronic pain became predictable based on the functional connectivity patterns. The results indicate changes in DMN activity and betweenness centrality HDI in chronic pain. The predictability of chronic pain using machine learning points to an information content in the connectivity patterns that has not yet been captured in conventional network analyses.

Cerebral ischemia/reperfusion (I/R) injury caused by resumed blood flow to an infarcted area contributes to poor patient prognosis due to a lack of treatment strategies. While the blood-brain barrier (BBB) is the greatest barrier for drug delivery to the brain, temporary disruption to the BBB after brain I/R injury allows for delivery of cerebroprotective drug-encapsulated nanoparticles into the brain parenchyma. However, issues remain with delivering drugs to the I/R region using nanoparticles, such as the limited therapeutic time window due to BBB repair over time. To overcome these challenges, we developed nanoparticles specifically targeting the I/R environment. Human umbilical vein endothelial cells (HUVECs) were exposed to oxygen-glucose deprivation/reoxygenation (OGD/R), an in vitro I/R model. Low-density lipoprotein receptor (LDLR) mRNA was upregulated early during the reoxygenation process. Furthermore, immunostaining of OGD/R-treated cells showed an increase in LDLR expression. Next, we constructed a peptide that mimics the LDLR binding recognition site on LDL, and modified liposomes to display the peptide on their surface. Peptide-modified liposomes showed targeting ability to the LDLR on cells. Accumulation of peptide-modified liposomes was significantly increased in OGD/R treated cells compared with controls, and was reduced by blocking LDLR using its antibody. These results demonstrate upregulation of LDLR and LDLR-mediated liposome uptake in OGD/R stressed cells. In conclusion, LDLR binding recognition site mimicking peptide-modified liposomes are a useful drug carrier that can recognize I/R injured endothelial cells.

Prenatal exposure to environmental chemicals, including pesticides, has been epidemiologically linked to neurodevelopmental disorders. Acetamiprid, a nicotine-mimetic insecticide, has been shown to cause neurotoxicity and abnormal neuronal distribution in rats. Furthermore, acetamiprid has been reported to activate microglia, the resident immune cells of the central nervous system, via a transition to an amoeboid shape with increased phagocytic activity in prenatally exposed neonatal mice. However, the impact of prenatal exposure to acetamiprid on offspring's microglial morphology and function remains inadequately understood. Here, we investigated the effects of prenatal exposure to acetamiprid on offspring microglial morphology and phagocytic function in response to ATP, which is released from distressed cells and results in microglial activation. We found that acetamiprid-exposed microglia significantly increased interleukin-1β (IL-1β) levels in both conditions, without and with ATP stimulation compared to microglia derived from offspring that were prenatally exposed to dimethyl sulfoxide or non-treated. In addition, microglia from offspring prenatally exposed to acetamiprid underwent morphological changes upon ATP stimulation. Given that elevated IL-1β levels are often accompanied by changes in phagocytic function, we next assessed phagocytosis under the same conditions. While phagocytosis was enhanced in the offspring prenatally exposed to acetamiprid, ATP failed to further induce phagocytic function. These findings suggest that prenatal exposure to acetamiprid enhances microglial activity but impairs the phagocytotic reactivity of offspring microglia to ATP stimulation. Further studies are needed to clarify the underlying mechanisms and potential neurodevelopmental consequences in humans.