Search Results (42)

Physical stimulation, which is a key factor affecting the metabolism of osteoblasts and their precursor cells, plays an important role in bone remodeling; however, the role of micro-vibrations in osteoblast differentiation is unclear. In the present study, we determined the effects of frequency-regulated repeated micro-vibration (FRMV) on cell proliferation and established a method to induce osteoblast differentiation through FRMV using the mouse pre-osteoblast-like cell line MC3T3-E1, which is widely used in bone metabolism research. The results indicated that FRMV significantly influenced the proliferation of MC3T3-E1 cells in a normal growth medium. FRMV at 42.2 Hz significantly promoted proliferation, whereas FRMV at 92.1 Hz showed no effect on the proliferation rate. Moreover, FRMV at 42.2 Hz significantly increased alkaline phosphatase (ALP) enzyme activity and ALP gene expression in MC3T3-E1 cells. Treatment with LDN193189, a bone morphogenetic protein (BMP) signaling inhibitor, revealed that the FRMV-induced upregulation in ALP enzyme activity and ALP gene expression were significantly suppressed in MC3T3-E1 cells. The results suggest that the FRMV protocol developed in the present study induces osteoblast differentiation through the BMP signaling pathway. Thus, FRMV may contribute to the development of effective bone regeneration technologies. Full article

In recent years, with the advent of a super-aged society, lifelong dental care has gained increasing emphasis, and implant therapy for patients with an edentulous jaw has become a significant option. However, for implant therapy to be suitable for elderly patients with reduced regenerative and immunological capabilities, higher osteoconductive and antimicrobial properties are required on the implant surfaces. Silicon nitride, a non-oxide ceramic known for its excellent mechanical properties and biocompatibility, has demonstrated high potential for inducing hard tissue differentiation and exhibiting antibacterial properties. In this study, silicon nitride was deposited on pure titanium metal surfaces and evaluated for its biocompatibility and antibacterial properties. The findings indicate that silicon nitride improves the hydrophilicity of the material surface, enhancing the initial adhesion of rat bone marrow cells and promoting hard tissue differentiation. Additionally, the antibacterial properties were assessed using Staphylococcus aureus, revealing that the silicon nitride-coated surfaces exhibited significant antibacterial activity. Importantly, no cytotoxicity was observed, suggesting that silicon nitride-coated titanium could serve as a novel implant material. Full article

Unresectable, metastatic, advanced urothelial carcinoma (aUC) is an aggressive disease and is treated with platinum-containing first-line chemotherapy, followed by immune checkpoint inhibitors and antibody–drug conjugates. Response to first-line chemotherapy is a vital priority in sequential treatment strategies because a better response to first-line chemotherapy is associated with a better response to subsequent therapies. Gemcitabine plus carboplatin chemotherapy is conventionally recommended for cisplatin-ineligible patients. This multicenter, single-arm prospective trial will investigate whether dose-dense methotrexate, vinblastine, doxorubicin, and carboplatin (DD-MVACarbo) chemotherapy is superior to gemcitabine plus carboplatin chemotherapy in terms of efficacy in platinum-naïve, cisplatin-ineligible patients with aUC. After screening and registration, a total of 46 patients will be treated with this novel chemotherapy regimen. The primary endpoint is the objective response rate. The secondary endpoints include disease control rate, patient-reported outcomes, and adverse events. No evidence of this novel intervention is available as of July 2024. The results are expected to change the standard of care and improve the management of patients with aUC. Full article

Over the years, the concentration of cadmium in soil has increased due to industrialization. Cadmium in the soil enters the human body through plant accumulation, seriously endangering human health. In the current study, two types of hydrogels were successfully synthesized using a free radical polymerization method: an ion-type hydrogel referred to as DMAPAA (N-(3-(Dimethyl amino) propyl) acrylamide)/DMAPAAQ (N,N-Dimethyl amino propyl acrylamide, methyl chloride quaternary) and a non-ion-type hydrogel known as DMAA (N,N-Dimethylacrylamide). In the experiment carried out in this study, the ion-type hydrogel DMAPAA/DMAPAAQ was introduced to cadmium-contaminated soil for vegetable cultivation. The study found that at cadmium levels of 0 and 2 mg/kg in soil, when exposed to a pH 2 solution, cadmium wasn’t detected in the filtrate using ICP. As the amount of cadmium increased to 500 mg/kg, hydrogel addition gradually reduced the filtrate cadmium concentration. Notably, the use of the 4% hydrogel resulted in 0 mg/L of cadmium. For the 0% hydrogel, vegetable cadmium absorption was determined to be 0.07 mg/g, contrasting with 0.03 mg/g for the 4% hydrogel. The DMAPAA/DMAPAAQ hydrogel significantly boosts vegetable growth by efficiently absorbing nitrate ions through ion exchange, releasing them for plant uptake. In contrast, the DMAA hydrogel, used as a control, does not enhance plant growth despite its water absorption properties. In summary, the composite hydrogel shows great potential for enhancing vegetable yield and immobilizing heavy metals in soil. Full article

To compare late renal effects in pediatric and adult patients with malignancies after PBT involving part of the kidney. A retrospective study was conducted to assess changes in renal volume and function in 24 patients, including 12 children (1–14 years old) and 12 adults (51–80 years old). Kidney volumes were measured from CT or MRI images during follow-up. Dose-volume histograms were calculated using a treatment planning system. In children, the median volume changes for the irradiated and control kidneys were −5.58 (−94.95 to +4.79) and +14.92 (−19.45 to +53.89) mL, respectively, with a relative volume change of −28.38 (−119.45 to −3.87) mL for the irradiated kidneys. For adults, these volume changes were −22.43 (−68.7 to −3.48) and −21.56 (−57.26 to −0.16) mL, respectively, with a relative volume change of −5.83 (−28.85 to +30.92) mL. Control kidneys in children exhibited a marked increase in size, while those in adults showed slight volumetric loss. The percentage of irradiated volume receiving 10 Gy (RBE) (V10) and 20 Gy (RBE) (V20) were significantly negatively associated with the relative volume change per year, especially in children. The CKD stage based on eGFR for all patients ranged from 1 to 3 and no cases with severe renal dysfunction were found before or after PBT. Late effects on the kidneys after PBT vary among age groups. Children are more susceptible than adults to significant renal atrophy after PBT. V10 and V20 might serve as predictors of the degree of renal atrophy after PBT, especially in children. PBT has a minimal impact on deterioration of renal function in both children and adults. Full article

Synovial sarcoma (SS), a rare subtype of soft-tissue sarcoma distinguished by expression of the fusion gene SS18-SSX, predominantly affects the extremities of young patients. Existing anticancer drugs have limited efficacy against this malignancy, necessitating the development of innovative therapeutic approaches. Given the established role of SS18-SSX in epigenetic regulation, we focused on bromodomain and extra-terminal domain protein (BET) inhibitors and epigenetic agents. Our investigation of the BET inhibitor ABBV-075 revealed its pronounced antitumor effects, inducing G1-phase cell-cycle arrest and apoptosis, in four SS cell lines. Notably, BET inhibitors exhibited regulatory control over crucial cell-cycle regulators, such as MYC, p21, CDK4, and CDK6. Additionally, RNA sequencing findings across the four cell lines revealed the significance of fluctuating BCL2 family protein expression during apoptotic induction. Notably, variations in the expression ratio of the anti-apoptotic factor BCLxL and the pro-apoptotic factor BIM may underlie susceptibility to ABBV-075. Additionally, knockdown of SS18-SSX, which upregulates BCL2, reduced the sensitivity to ABBV-075. These findings suggest the potential utility of BET inhibitors targeting the SS18-SSX-regulated intrinsic apoptotic pathway as a promising therapeutic strategy for SS. Full article

PC12 cells, which are derived from rat adrenal pheochromocytoma cells, are widely used for the study of neuronal differentiation. NGF induces neuronal differentiation in PC12 cells by activating intracellular pathways via the TrkA receptor, which results in elongated neurites and neuron-like characteristics. Moreover, the differentiation requires both the ERK1/2 and p38 MAPK pathways. In addition to NGF, BMPs can also induce neuronal differentiation in PC12 cells. BMPs are part of the TGF-β cytokine superfamily and activate signaling pathways such as p38 MAPK and Smad. However, the brief lifespan of NGF and BMPs may limit their effectiveness in living organisms. Although PC12 cells are used to study the effects of various physical stimuli on neuronal differentiation, the development of new methods and an understanding of the molecular mechanisms are ongoing. In this comprehensive review, we discuss the induction of neuronal differentiation in PC12 cells without relying on NGF, which is already established for electrical, electromagnetic, and thermal stimulation but poses a challenge for mechanical, ultrasound, and light stimulation. Furthermore, the mechanisms underlying neuronal differentiation induced by physical stimuli remain largely unknown. Elucidating these mechanisms holds promise for developing new methods for neural regeneration and advancing neuroregenerative medical technologies using neural stem cells. Full article

This study aims to solve the problem of cadmium heavy metal ion pollution caused by the abuse of chemical fertilizers and activities such as mining, which pose a serious threat to the plant growth environment. We successfully synthesized DMAPAA (N-(3-(Dimethyl amino) propyl) acrylamide)/DMAPAAQ (N, N-Dimethyl amino propyl acrylamide, methyl chloride quaternary) hydrogels via free radical polymerization. Subsequently, we conducted experiments on this hydrogel for growing vegetables under cadmium stress conditions in aqueous solutions and soil. The cadmium capture capacity of DMAPAA/DMAPAAQ hydrogels under different cadmium ion concentrations and pH values was evaluated by using inductively coupled plasma optical emission spectrometry (ICP). The research results show that under the condition of pH = 7.3, the cadmium capture capacity of DMAPAA/DMAPAAQ hydrogels is the greatest. We used the Langmuir model to fit the adsorption data, and the correlation coefficient was as high as 0.96, indicating that the model fits well. The application of the hydrogels promoted the growth of vegetables in soil under cadmium stress conditions. The results showed that when the added amount of hydrogel was 4%, the dry weight of the vegetables was the largest. In addition, when the added amount of cadmium was 500 mg/kg and the added amount of hydrogel was 4%, the absorption of cadmium by the vegetables decreased to an undetectable level. In summary, the hydrogel successfully synthesized in this study can be effectively used to immobilize cadmium ions in soil while positively promoting the growth and yield of vegetables. This achievement has practical significance for solving the problem of heavy metal ion pollution. Full article

Sodium ions are commonly found in natural water sources, and their high concentrations can potentially lead to adverse effects on both the water sources and soil quality. In this study, we successfully synthesized potassium polyacrylate (KMAA) hydrogel through free radical polymerization and evaluated its capability to remove sodium ions from and supply potassium ions to aqueous solutions. To assess its performance, inductively coupled plasma emission spectroscopy (ICP) was employed to analyze the sodium ion removal capacity and potassium ion exchange capability of the KMAA hydrogel at various initial sodium ion concentrations and pH values. The results demonstrated that the KMAA hydrogel exhibited remarkable efficiency in removing sodium ions and providing potassium ions. At pH 7, the maximum adsorption capacity for sodium ions was measured at 70.7 mg·g⁻¹. The Langmuir model, with a correlation coefficient of 0.98, was found to be more suitable for describing the adsorption process of sodium ions. Moreover, at pH 4, the maximum exchange capacity for potassium ions reached 243.7 mg·g⁻¹. The Freundlich model, with a correlation coefficient of 0.99, was deemed more appropriate for characterizing the ion exchange behavior of potassium ions. In conclusion, the successfully synthesized KMAA hydrogel demonstrates superior performance in removing sodium ions and supplying potassium ions, providing valuable insights for addressing high sodium ion concentrations in water sources and facilitating potassium fertilizer supply. Full article

Sarcoma is a rare type of cancer for which new therapeutic agents are required. Ferroptosis is a nonapoptotic cell death triggered by iron-mediated lipid peroxidation. We found that TFRC, an iron uptake protein, was expressed at higher levels in sarcoma cell lines than in noncancer and carcinoma cell lines. Glutathione peroxidase 4 (GPX4) protects cells against ferroptosis, and its inhibition using RAS-selective lethal 3 (RSL3) had an antitumor effect that was more pronounced in sarcoma cell lines, particularly synovial sarcoma cells, compared to non-sarcoma cells. Because NF-κB can provoke ferroptosis, we examined the role of SHARPIN, an activator of NF-κB, in sarcoma. We found that SHARPIN expression was significantly associated with reduced survival in cohorts of patients with cancer, including sarcoma. In addition, SHARPIN promoted the sensitivity of sarcoma cells to ferroptosis. Further analyses revealed that the PGC1α/NRF2/SLC7A11 axis and BNIP3L/NIX-mediated mitophagy are regulated through NF-κB and PRMT5 downstream of SHARPIN. Our findings suggest that ferroptosis could have a therapeutic effect in sarcoma, particularly in subpopulations with high TFRC and SHARPIN expression. Full article

This study evaluated the mechanism of temperature-controlled repeated thermal stimulation (TRTS)-mediated neuronal differentiation. We assessed the effect of SP600125, a c-Jun N-terminal kinase (JNK) inhibitor, on neuronal differentiation of rat PC12-P1F1 cells, which can differentiate into neuron-like cells by exposure to TRTS or neurotrophic factors, including bone morphogenetic protein (BMP) 4. We evaluated neuritogenesis by incubating the cells under conditions of TRTS and/or SP600125. Cotreatment with SP600125 significantly enhanced TRTS-mediated neuritogenesis, whereas that with other selective mitogen-activated protein kinase (MAPK) inhibitors did not—e.g., extracellular signal-regulated kinase (ERK)1/2 inhibitor U0126, and p38 MAPK inhibitor SB203580. We tried to clarify the mechanism of SP600125 action by testing the effect of U0126 and the BMP receptor inhibitor LDN193189 on the SP600125-mediated enhancement of intracellular signaling. SP600125-enhanced TRTS-induced neuritogenesis was significantly inhibited by U0126 or LDN193189. Gene expression analysis revealed that TRTS significantly increased β3-Tubulin, MKK3, and Smad7 gene expressions. Additionally, Smad6 and Smad7 gene expressions were substantially attenuated through SP600125 co-treatment during TRTS. Therefore, SP600125 may partly enhance TRTS-induced neuritogenesis by attenuating the negative feedback loop of BMP signaling. Further investigation of the mechanisms underlying the effect of SP600125 during TRTS-mediated neuritogenesis may contribute to the future development of regenerative neuromedicine. Full article

Heated tobacco products are devices that deliver nicotine into the body via inhalation of the mainstream aerosols generated during direct and/or indirect heating of tobacco leaf material. Ammonia in aerosols potentially increases the alkalinity and, therefore, the proportion of free nicotine for easy absorption. Meanwhile, ammonia can be a cause of adverse health effects when involved in the aerosols. This study aimed to grasp the emission behaviour of ammonia in the mainstream aerosols generated from four kinds of devices that employ different heating temperatures from 40 to 350 °C. The aerosols were generated by a vaping machine following the CRM 81 puffing protocol. Ammonia in the forms of gas and particles was trapped in 5 mM oxalic acid and subsequently determined by ion chromatography. The results showed that the total emission amount of ammonia increased with an increase in the heating temperature regardless of the device used. The gas-particle distribution of ammonia also depended on the heating temperature; gaseous ammonia was only found in the device with 40 °C of the heating temperature. These results show that ammonia in the mainstream aerosols was emitted from a common thermal process, probably thermal extraction in water vapour from a tobacco leaf. Full article

Increased research attention is being given to bacterial diversity associated with lichens. Rock tripe lichens (Umbilicariaceae) were collected from two distinct Antarctic biological regions, the continental region near the Japanese Antarctic station (Syowa Station) and the maritime Antarctic South Orkney Islands (Signy Island), in order to compare their bacterial floras and potential metabolism. Bulk DNA extracted from the lichen samples was used to amplify the 18S rRNA gene and the V3-V4 region of the 16S rRNA gene, whose amplicons were Sanger- and MiSeq-sequenced, respectively. The fungal and algal partners represented members of the ascomycete genus Umbilicaria and the green algal genus Trebouxia, based on 18S rRNA gene sequences. The V3-V4 sequences were grouped into operational taxonomic units (OTUs), which were assigned to eight bacterial phyla, Acidobacteriota, Actinomyceota, Armatimonadota, Bacteroidota, Cyanobacteria, Deinococcota, Pseudomonadota and the candidate phylum Saccharibacteria (also known as TM7), commonly present in all samples. The OTU floras of the two biological regions were clearly distinct, with regional biomarker genera, such as Mucilaginibacter and Gluconacetobacter, respectively. The OTU-based metabolism analysis predicted higher membrane transport activities in the maritime Antarctic OTUs, probably influenced by the sampling area’s warmer maritime climatic setting. Full article

Although children with developmental coordination disorder (DCD) show impaired precision grip control due to a sensory-motor integration deficit, their spatial instability (such as changes in force direction and object roll during a precision grip task) is unclear. Herein, we investigated the spatial instability in the precision grip force control of children with poor manual dexterity. We divided 66 school-aged children who performed a precision gripping and lifting of heavy- or lightweight objects into those with low manual dexterity (n = 11) and those with high manual dexterity (n = 55) as revealed by the Movement Assessment Battery for Children (2nd edition). The group and weight effects were then determined. The results revealed that the total trajectory lengths of the center of pressure (COP) were longer in the lightweight object data of the children in the low-manual-dexterity group and were related to the children’s grip force. The low-manual-dexterity group also showed a shifted COP position from the center of the object in the medial–lateral direction and in the object roll regardless of the object’s weight; these were closely related in both weights’ tests. These results demonstrated that children with poor manual dexterity show spatial instability and different adaptations to the weight of objects during a precision grip task. Further studies are needed to determine whether these findings would be replicated in children with a diagnosis of DCD. Full article

The Gly16Arg polymorphism results in a G to C nucleotide mutation in the human beta 2-adrenergic receptor (ADRB2) gene and has a relationship with obesity; however, this substitution’s effects on food preferences are unclear. Therefore, we determined this relationship among healthy young adults (mean age, 23.4; n = 52). To evaluate food preferences, four categories of food (sweet, salty, sour, and bitter) along with high-fat foods were evaluated using a self-reporting questionnaire. Male (n = 26) and female subjects (n = 26) were genotyped for the polymorphism and further divided into three groups (two homozygous groups, GG, CC; and a heterozygous group, GC). Preference for sour foods in the GG group was higher compared with that in the CC group in females (p < 0.05). When sweet foods were classified into low- and high-fat subgroups, preference for high-fat sweet foods in the GG group was higher than that for low-fat sweet foods in all subjects (p < 0.05). The degree of preference for high-fat foods in the GG group was higher than other groups for males (p < 0.05). These results suggest that ADRB2 polymorphism is associated with food preference. Understanding the relationship of ADRB2 substitution to food preference will be valuable for designing individualized anti-obesity strategies. Full article