Far-infrared radiation and its therapeutic parameters: A superior alternative for future regenerative medicine?

In future regenerative medicine, far-infrared radiation (FIR) may be an essential component of optical therapy. Many studies have confirmed or validated the efficacy and safety of FIR in various diseases, benefiting from new insights into FIR mechanisms and the excellent performance of many applications. However, the lack of consensus on the biological effects and therapeutic parameters of FIR limits its practical applications in the clinic. In this review, the definition, characteristics, and underlying principles of the FIR are systematically illustrated. We outline the therapeutic parameters of FIR, including the wavelength range, power density, irradiation time, and distance. In addition, the biological effects, potential molecular mechanisms, and preclinical and clinical applications of FIR are discussed. Furthermore, the future development and applications of FIR are described in this review. By applying optimal therapeutic parameters, FIR can influence various cells, animal models, and patients, eliciting diverse underlying mechanisms and offering therapeutic potential for many diseases. FIR could represent a superior alternative with broad prospects for application in future regenerative medicine.

An Innovative Design to Enhance Osteoinductive Efficacy and Biomechanical Behavior of a Titanium Dental Implant.

The present study investigated the in vivo bone-forming efficacy of an innovative titanium (Ti) dental implant combined with a collagen sponge containing recombinant human bone morphogenetic protein-2 (BMP-2) in a pig model. Two different concentrations of BMP-2 (20 and 40 µg/mL) were incorporated into collagen sponges and placed at the bottom of Ti dental implants. The investigated implants were inserted into the edentulous ridge at the canine-premolar regions of Lanyu small-ear pigs, which were then euthanized at weeks 1, 2, 4, 8, and 12 post-implantation. Specimens containing the implants and surrounding bone tissue were collected for histological evaluation of their bone-to-implant contact (BIC) ratios and calculation of maximum torques using removal torque measurement. Analytical results showed that the control and BMP-2-loaded implants presented good implant stability and bone healing for all testing durations. After 1 week of healing, the BMP-2-loaded implants with a concentration of 20 µg/mL exhibited the highest BIC ratios, ranging from 58% to 76%, among all groups (p = 0.034). Additionally, they also possessed the highest removal torque values (50.1 ± 1.3 N-cm) throughout the 8-week healing period. The BMP-2-loaded implants not only displayed excellent in vivo biocompatibility but also presented superior osteoinductive performance. Therefore, these findings demonstrate that BMP-2 delivered through a collagen sponge can potentially enhance the early-stage osseointegration of Ti dental implants.

Nacre-Mimetic Structure Multifunctional Ion-Conductive Hydrogel Strain Sensors with Ultrastretchability, High Sensitivity, and Excellent Adhesive Properties.

Recently, conductive hydrogels have emerged as promising materials for smart, wearable devices. However, limited mechanical properties and low sensitivity greatly restrict their lifespan. Based on the design of biomimetic-layered structure, the conductive hydrogels with nacre-mimetic structure were prepared by using layered acrylic bentonite (AABT) and phytic acid (PA) as multifunctional "brick" and "mortar" units. Among them, the unique rigid cyclic multihydroxyl structure of the "organic mortar" PA preserves both ultrastretchability (4050.02%) and high stress (563.20 kPa) of the hydrogel, which far exceeds most of the reported articles. Because of the synergistic effect of AABT and PA, the hydrogel exhibits an excellent adhesive strength (87.74 kPa). The role of AABT in the adhesive properties of hydrogels is proposed for the first time, and a general strategy for improving the adhesive properties of hydrogels by using AABT is demonstrated. Furthermore, AABT provides ion channels and PA ionizes abundant H+, conferring a high gauge factor (GF = 14.95) and excellent antimicrobial properties to the hydrogel. Also, inspired by fruit batteries, simple self-powered flexible sensors were developed. Consequently, this study provides knowledge for functional bentonite filler modified hydrogel, and the prepared multifunctional ionic conductive hydrogel shows great application potential in the field of intelligent wearable devices.

Model averaging estimation of panel data models with many instruments and boosting.

Applied researchers often confront two issues when using the fixed effect-two-stage least squares (FE-2SLS) estimator for panel data models. One is that it may lose its consistency due to too many instruments. The other is that the gain of using FE-2SLS may not exceed its loss when the endogeneity is weak. In this paper, an L2Boosting regularization procedure for panel data models is proposed to tackle the many instruments issue. We then construct a Stein-like model-averaging estimator to take advantage of FE and FE-2SLS-Boosting estimators. Finite sample properties are examined in Monte Carlo and an empirical application is presented.

Biomechanical stress distribution of medical inelastic fabrics with different porosity structures.

Clothing fit and pressure comfort play important role in clothing comfort, especially in medical body sculpting clothing (MBSC). In the present study, different body movements (forward bending, side bending, and twisting) were adopted to simulate and investigate the biomechanical stress distribution of the human body with three kinds of porosity inelastic MBSCs through the finite element analysis method. The elastic modulus of the investigated MBSCs was also measured by means of tensile testing. Analytical results showed that in the compression region during body movements, the investigated inelastic MBSCs endured less compression stress, and most of the stress was transmitted to the human body. Moreover, the stresses on the body surface were decreased with the porosity increasing. However, most of the von Mises stresses on the human body were in the desired pressure comfort range. Therefore, these results could provide potential information in the modification of MBSC for medical applications.

An Innovative Biofunctional Composite Hydrogel with Enhanced Printability, Rheological Properties, and Structural Integrity for Cell Scaffold Applications.

The present study was conducted to manipulate various biomaterials to find potential hydrogel formulations through three-dimensional (3D) bioprinting fabrication for tissue repair, reconstruction, or regeneration. The hydrogels were prepared using sodium alginate and gelatin combined with different concentrations of Pluronic F127 (6% (3 g), 8% (4 g), and 10% (5 g)) and were marked as AGF-6%, AGF-8%, and AGF-10%, respectively. The properties of the hydrogels were investigated using a contact angle goniometer, rheometer, and 3D bioprinter. In addition, the osteoblast-like cell line (MG-63) was used to evaluate the cell viability including hydrogels before and after 3D bioprinting. It was found that the ratio of contact angle was lowest at AGF-6%, and the rheological results were higher for all samples of AGF-6%, AGF-8%, and AGF-10% compared with the control sample. The printability indicated that the AGF-6% hydrogel possessed great potential in creating a cell scaffold with shape integrity. Moreover, the live/dead assay also presented the highest numbers of live cells before printing compared with after printing. However, the number of live cells on day 7 was higher than on day 1 before and after printing (** p < 0.01). Therefore, the combination of AGF-6% could be developed as a biofunctional hydrogel formulation for potential tissue regeneration applications.

Age-related self-DNA accumulation may accelerate arthritis in rats and in human rheumatoid arthritis.

The incidence of rheumatoid arthritis (RA) is increasing with age. DNA fragments is known to accumulate in certain autoimmune diseases, but the mechanistic relationship among ageing, DNA fragments and RA pathogenesis remain unexplored. Here we show that the accumulation of DNA fragments, increasing with age and regulated by the exonuclease TREX1, promotes abnormal activation of the immune system in an adjuvant-induced arthritis (AIA) rat model. Local overexpression of TREX1 suppresses synovial inflammation in rats, while conditional genomic deletion of TREX1 in AIA rats result in higher levels of circulating free (cf) DNA and hence abnormal immune activation, leading to more severe symptoms. The dysregulation of the heterodimeric transcription factor AP-1, formed by c-Jun and c-Fos, appear to regulate both TREX1 expression and SASP induction. Thus, our results confirm that DNA fragments are inflammatory mediators, and TREX1, downstream of AP-1, may serve as regulator of cellular immunity in health and in RA.

Adenosine 2A receptor contributes to the facilitation of post-infectious irritable bowel syndrome by γδ T cells via the PKA/CREB/NF-κB signaling pathway.

BACKGROUND: Immunological dysfunction-induced low-grade inflammation is regarded as one of the predominant pathogenetic mechanisms in post-infectious irritable bowel syndrome (PI-IBS). γδ T cells play a crucial role in innate and adaptive immunity. Adenosine receptors expressed on the surface of γδ T cells participate in intestinal inflammation and immunity regulation. AIM: To investigate the role of γδ T cell regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: The PI-IBS mouse model has been established with Trichinella spiralis (T. spiralis) infection. The intestinal A2AR and A2AR in γδ T cells were detected by immunohistochemistry, and the inflammatory cytokines were measured by western blot. The role of A2AR on the isolated γδ T cells, including proliferation, apoptosis, and cytokine production, were evaluated in vitro. Their A2AR expression was measured by western blot and reverse transcription polymerase chain reaction (RT-PCR). The animals were administered with A2AR agonist, or A2AR antagonist. Besides, γδ T cells were also injected back into the animals, and the parameters described above were examined, as well as the clinical features. Furthermore, the A2AR-associated signaling pathway molecules were assessed by western blot and RT-PCR. RESULTS: PI-IBS mice exhibited elevated ATP content and A2AR expression (P < 0.05), and suppression of A2AR enhanced PI-IBS clinical characteristics, indicated by the abdominal withdrawal reflex and colon transportation test. PI-IBS was associated with an increase in intestinal T cells, and cytokine levels of interleukin-1 (IL-1), IL-6, IL-17A, and interferon-α (IFN-α). Also, γδ T cells expressed A2AR in vitro and generated IL-1, IL-6, IL-17A, and IFN-α, which can be controlled by A2AR agonist and antagonist. Mechanistic studies demonstrated that the A2AR antagonist improved the function of γδ T cells through the PKA/CREB/NF-κB signaling pathway. CONCLUSION: Our results revealed that A2AR contributes to the facilitation of PI-IBS by regulating the function of γδ T cells via the PKA/CREB/NF-κB signaling pathway.

The effectiveness of mindfulness-based cognitive therapy combined with medication therapy in preventing recurrence of major depressive disorder in convalescent patients.

Objective: This study aims to investigate the effectiveness of mindfulness-based cognitive therapy (MBCT) combined with medication therapy in preventing the recurrence of major depressive disorder (MDD) in convalescent patients. Methods: A total of 130 patients with convalescent MDD were enrolled in this prospective study. Sixty-five patients were assigned to the experimental group and received medication therapy combined with MBCT, and 65 patients were assigned to the control group and treated with medication alone. The recurrence rate and related hormonal changes were compared between the two groups. Results: After 1 year of MBCT intervention, eight patients experienced recurrence in the experimental group, a recurrence rate of 12.31%, and 19 patients experienced recurrence in the control group, a recurrence rate of 29.23%. The Hamilton Depression Rating Scale (HAM-D) and the World Health Organization Quality of Life Scale (WHOQOL-BREF) scores in both the experimental and the control groups were significantly improved after treatment (P < 0.05). The difference in the HAM-D scores before and after treatment in the experimental group was 16.74 ± 4.54; this was significantly higher than that of the control group (8 ± 3.89, P < 0.0001). The WHOQOL-BREF scores in the experimental group were significantly improved compared with those of the control group (P < 0.0001). The differences in the levels of corticotrophin-releasing hormone (CRH), adrenocorticotropic hormone, and cortisol before and after treatment in the experimental group and the control group were statistically significant (P < 0.05). The difference in CRH before and after treatment in the experimental group was 16.8 ± 7.2, which was higher than that of the control group (2.75 ± 9.27, P < 0.0001). The intervention with MBCT had a significant impact on the recurrence of MDD [ß = 1.206, P = 0.039, 95% (confidence interval) CI = 0.0790-1.229]. The difference in the HAM-D scores also had a significant impact on the recurrence of MDD (ß = 1.121, P = 0.0014, 95% CI = 0.805-0.976). Conclusion: Compared with medication therapy alone, the use of MBCT combined with medication therapy can effectively prevent the recurrence of MDD in convalescent patients.

Changes in the psychological defense mechanism and clinical features of patients with OCD - A four-year follow-up study.

OBJECTIVE: The present study aims to (1) follow up with 4-year changes in the efficacy outcome, defense style questionnaire (DSQ) score, and clinical features of patients with obsessive-compulsive disorder (OCD) and (2) analyze the relationship between different levels of efficacy and changes in the patients' psychological defense mechanisms. METHODS: The following data collection and 4-year follow-up were completed for 153 patients with OCD: (1) the treatment process, efficacy outcome, course of disease, and clinical features of OCD were collected using a self-made general information questionnaire and (2) the control method was used to analyze the changes in clinical symptoms (Yale-Brown obsessive compulsive scale [YBOCS], Hamilton anxiety score [HAMA], and Hamilton depression scale [HAMD]) in patients with OCD. Moreover, the changes in the psychological defense mechanism (measured by DSQ) and the relation between the prognosis and DSQ score were investigated. RESULTS: (1) The HAMA score (8.7 ±â€¯4.8 points), HAMD score (12.0 ±â€¯6.6 points) and YBOCS score (16.4 ±â€¯8.4 points) were significantly lower during the follow-up than at the time of enrollment (p < 0.01). In the two DSQ evaluations, there were no significant differences in the factors, with the exception of a significant decrease in the use of "reaction formation" (t = 2.533, p = 0.015). The changes of mature defense factors in the significant efficacy group significantly increased (p < 0.01). Which was mainly manifested in the significant increase in the score of "sublimation" item, and the difference was extremely significant (t = -3.093, p = 0.006). CONCLUSION: An abnormal psychological defense mechanism plays an important role in OCD, and the use of a mature defense mechanism is significantly related to the treatment efficacy.

A Three-Dimensional Bioprinted Copolymer Scaffold with Biocompatibility and Structural Integrity for Potential Tissue Regeneration Applications.

The present study was to investigate the rheological property, printability, and cell viability of alginate−gelatin composed hydrogels as a potential cell-laden bioink for three-dimensional (3D) bioprinting applications. The 2 g of sodium alginate dissolved in 50 mL of phosphate buffered saline solution was mixed with different concentrations (1% (0.5 g), 2% (1 g), 3% (1.5 g), and 4% (2 g)) of gelatin, denoted as GBH-1, GBH-2, GBH-3, and GBH-4, respectively. The properties of the investigated hydrogels were characterized by contact angle goniometer, rheometer, and bioprinter. In addition, the hydrogel with a proper concentration was adopted as a cell-laden bioink to conduct cell viability testing (before and after bioprinting) using Live/Dead assay and immunofluorescence staining with a human corneal fibroblast cell line. The analytical results indicated that the GBH-2 hydrogel exhibited the lowest loss rate of contact angle (28%) and similar rheological performance as compared with other investigated hydrogels and the control group. Printability results also showed that the average wire diameter of the GBH-2 bioink (0.84 ± 0.02 mm (*** p < 0.001)) post-printing was similar to that of the control group (0.79 ± 0.05 mm). Moreover, a cell scaffold could be fabricated from the GBH-2 bioink and retained its shape integrity for 24 h post-printing. For bioprinting evaluation, it demonstrated that the GBH-2 bioink possessed well viability (>70%) of the human corneal fibroblast cell after seven days of printing under an ideal printing parameter combination (0.4 mm of inner diameter needle, 0.8 bar of printing pressure, and 25 °C of printing temperature). Therefore, the present study suggests that the GBH-2 hydrogel could be developed as a potential cell-laden bioink to print a cell scaffold with biocompatibility and structural integrity for soft tissues such as skin, cornea, nerve, and blood vessel regeneration applications.

Upregulated adenosine 2A receptor accelerates post-infectious irritable bowel syndrome by promoting CD4+ T cells' T helper 17 polarization.

BACKGROUND: Post-infectious irritable bowel syndrome (PI-IBS) is generally regarded as a functional disease. Several recent studies have reported the involvement of low-grade inflammation and immunological dysfunction in PI-IBS. T helper 17 (Th17) polarization occurs in IBS. Adenosine and its receptors participate in intestinal inflammation and immune regulation. AIM: To investigate the role of Th17 polarization of CD4+ T cells regulated by adenosine 2A receptor (A2AR) in PI-IBS. METHODS: A PI-IBS model was established by infecting mice with Trichinella spiralis. The intestinal A2AR and CD4+ T lymphocytes were detected by immunohistochemistry, and the inflammatory cytokines were detected by enzyme-linked immunoassay. CD4+ T lymphocytes present in the animal's spleen were separated and cultured with or without A2AR agonist and antagonist. Western blotting and real-time quantitative polymerase chain reaction were performed to determine the effect of A2AR on the cells and intestinal tissue. Cytokine production was determined. The protein and mRNA levels of A2AR associated signaling pathway molecules were also evaluated. Furthermore, A2AR agonist and antagonist were injected into the mouse model and the clinical features were observed. RESULTS: The PI-IBS mouse model showed increased expression of ATP and A2AR (P < 0.05), and inhibition of A2AR improved the clinical features in PI-IBS, including the abdominal withdrawal reflex and colon transportation test (P < 0.05). The number of intestinal CD4+ T cells and interleukin-17 (IL-17) protein levels increased during PI-IBS, which was reversed by administration of the A2AR antagonist (P < 0.05). CD4+ T cells expressed A2AR and produced IL-17 in vitro, which was regulated by the A2AR agonist and antagonist. The A2AR antagonist increased the production of IL-17 by CD4+ T cells via the Janus kinase-signal transducer and activator of transcription-receptor-related orphan receptor γ signaling pathway. CONCLUSION: The results of the present study suggested that the upregulation of A2AR increases PI-IBS by promoting the Th17 polarization of CD4+ T cells.

A pilot study: Gut microbiota, metabolism and inflammation in hypertensive intracerebral haemorrhage.

AIMS: In recent years, the incidence rate of hypertensive intracerebral haemorrhage (HICH) has been increasing, accompanied by high mortality and morbidity, which has brought a heavy burden to the social economy. However, the pathogenesis of HICH is still unclear. This study intends to explore the mechanism of gut microbiota metabolism and inflammation in the process of HICH to provide a theoretical basis for the diagnosis and treatment of HICH. METHODS AND RESULTS: HE staining showed that the brain tissues of model group had obvious oedema injury, which indicated that the HICH model was successfully constructed. ELISA analysis showed that IL-1ß and TNF-α levels in blood and brain tissues were significantly increased, and IL-10 level was significantly decreased in blood. IHC analysis showed that microglia and macrophages were activated in the model group. 16S rRNA sequence showed that the diversity of gut microbiota in HICH patients decreased. Also, the microbiota belonging to Firmicutes, Proteobacteria and Verrucomicrobia changed significantly. LC-MS/MS analysis showed that the metabolic phenotype of HICH patients changed. Also, the 3,7-dimethyluric acid- and 7-methylxanthine-related metabolic pathways of caffeine metabolism pathways were downregulated in patients with HICH. Bacteroides was negatively correlated with the IL-1ß and TNF-α levels. Blautia was negatively correlated with the IL-1ß and TNF-α levels, and positively correlated with the IL-10 level. Akkermansia was negatively correlated with the 3,7-dimethyluric acid and 7-methylxanthine. CONCLUSION: Our study suggested that HICH was accompanied by the increased inflammation marker levels in peripheral blood and brain, decreased gut microbiota diversity, altered gut metabolic phenotype and downregulation of caffeine metabolism pathway. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study reported that HICH accompanied by the increased inflammation, decreased gut microbiota diversity and altered gut metabolic phenotype. Due to the number of patients, this work was a pilot study.

Three-Dimensional Printing of a Hybrid Bioceramic and Biopolymer Porous Scaffold for Promoting Bone Regeneration Potential.

In this study, we proposed a three-dimensional (3D) printed porous (termed as 3DPP) scaffold composed of bioceramic (beta-tricalcium phosphate (ß-TCP)) and thermoreversible biopolymer (pluronic F-127 (PF127)) that may provide bone tissue ingrowth and loading support for bone defect treatment. The investigated scaffolds were printed in three different ranges of pore sizes for comparison (3DPP-1: 150−200 µm, 3DPP-2: 250−300 µm, and 3DPP-3: 300−350 µm). The material properties and biocompatibility of the 3DPP scaffolds were characterized using scanning electron microscopy, X-ray diffractometry, contact angle goniometry, compression testing, and cell viability assay. In addition, micro-computed tomography was applied to investigate bone regeneration behavior of the 3DPP scaffolds in the mini-pig model. Analytical results showed that the 3DPP scaffolds exhibited well-defined porosity, excellent microstructural interconnectivity, and acceptable wettability (θ < 90°). Among all groups, the 3DPP-1 possessed a significantly highest compressive force 273 ± 20.8 Kgf (* p < 0.05). In vitro experiment results also revealed good cell viability and cell attachment behavior in all 3DPP scaffolds. Furthermore, the 3DPP-3 scaffold showed a significantly higher percentage of bone formation volume than the 3DPP-1 scaffold at week 8 (* p < 0.05) and week 12 (* p < 0.05). Hence, the 3DPP scaffold composed of ß-TCP and F-127 is a promising candidate to promote bone tissue ingrowth into the porous scaffold with decent biocompatibility. This scaffold particularly fabricated with a pore size of around 350 µm (i.e., 3DPP-3 scaffold) can provide proper loading support and promote bone regeneration in bone defects when applied in dental and orthopedic fields.

A study on diffusion tensor imaging in patients with untreated first-episode obsessive-compulsive disorder.

OBJECTIVE: The present study provides an overview of studies investigating white matter (WM) integrity in patients with obsessive-compulsive disorder (OCD) using diffusion tensor imaging (DTI). Furthermore, it studies the correlation of fractional anisotropy (FA) in abnormal cerebral WM areas with the course and clinical signs of the disease. METHODS: The study subjects were divided into two groups, the OCD group (n=38) and the control group (n=40), based on the Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-5) diagnostic criteria for OCD. Patients with untreated first-episode OCD were assigned to the OCD group, while healthy volunteers were assigned to the control group. The study group was evaluated in accordance with the Yale-Brown Obsessive-Compulsive Scale (Y-BOCS), Self-Rating Depression Scale (SDS) and Self-Rating Anxiety Scale (SAS). Subjects who met the inclusion criteria underwent whole-brain scanning via 3.0 T structural magnetic resonance imaging (sMRI). The WM FA values in different brain areas were compared between the two groups using voxel-based analysis (VBA). Subsequently, the correlations of the patient Y-BOCS score and disorder course with the FA values in significantly improved encephalic areas were analyzed. RESULTS: (I) The FA values of the right precentral gyrus (PreCG.R), left insular lobe, left inferior frontal gyrus and right inferior occipital gyrus (Occipital_Inf_R) WM were significantly lower in the OCD group than in the control group (P<0.05). Elevated FA values were not observed in the OCD group. (II) FA values of PreCG.R, left insular lobe/left inferior frontal gyrus, and Occipital_Inf_R were not found in relation to the total Y-BOCS score (P=0.122; P=0.401; P=0.134), obsessional thoughts score (P=0.299; P=0.760; P=0.062), compulsive activities checklist (P=0.487; P=0.420; P=0.431), and disease course (P=0.604; P=0.380; P=0.182). CONCLUSIONS: Multiple microstructural cerebral WM changes were observed in the frontal lobe, occipital lobe, and insula in patients with untreated first-episode OCD, presenting the correlation of these changes with OCD occurrence.

An Innovative Customized Biomimetic Hydrogel for Drug Screening Application Potential: Biocompatibility and Cell Invasion Ability.

The ability of Pluronic F127 (PF127) conjugated with tetrapeptide Gly-Arg-Gly-Asp (GRGD) as a sequence of Arg-Gly-Asp (RGD) peptide to form the investigated potential hydrogel (hereafter referred to as 3DG bioformer (3BE)) to produce spheroid, biocompatibility, and cell invasion ability, was assessed in this study. The fibroblast cell line (NIH 3T3), osteoblast cell line (MG-63), and human breast cancer cell line (MCF-7) were cultured in the 3BE hydrogel and commercial product (Matrigel) for comparison. The morphology of spheroid formation was evaluated via optical microscopy. The cell viability was observed through cell counting Kit-8 assay, and cell invasion was investigated via Boyden chamber assay. Analytical results indicated that 3BE exhibited lower spheroid formation than Matrigel. However, the 3BE appeared biocompatible to NIH 3T3, MG-63, and MCF-7 cells. Moreover, cell invasion ability and cell survival rate after invasion through the 3BE was displayed to be comparable to Matrigel. Thus, these findings demonstrate that the 3BE hydrogel has a great potential as an alternative to a three-dimensional cell culture for drug screening applications.

4,5-Dimethoxycanthin-6-one is a novel LSD1 inhibitor that inhibits proliferation of glioblastoma cells and induces apoptosis and pyroptosis.

BACKGROUND: Glioblastoma is one of the most common fatal intracranial malignancies. Lysine-specific demethylase 1 (LSD1) reportedly has therapeutic effects on a variety of tumors. This study explored the therapeutic effect of LSD1 inhibition on glioblastoma cell lines and the possible underlying mechanisms. METHODS: The MTT assay was utilized to screen for the sensitivity of U87, U251 and T98G cells to 4, 5-dimethoxycarrageenin-6-one. qRT-PCR and western blot were used to measure the proliferation, apoptosis, and pyroptosis signaling pathway expression to observe the effect of LSD1 inhibition on U251 and T98G cells. Flow cytometry, immunofluorescence, immunohistochemistry, wound scratch, clone formation, and TUNEL assay were used to analyze the effects of 4, 5-dimethoxycanthin-6-one on glioblastoma cells. The effect of 4, 5-dimethoxycanthin-6-one was examined in vivo in BALB/c nude mice injected with U251 cells. HE staining was used to detect the histopathology of the tumor. RESULTS: LSD1 specifically catalyzes the demethylation of monomethylated and demethylated histone H3 lysine at position 4 (h3k4me1, h3k4me2, h3k4me3) and lysine at position 9 (h3k9me1). This regulated the transcriptional activity of proliferation, apoptosis, and pyroptosis signaling pathway genes. In vitro, the proliferation of glioblastoma cells was decreased in the 4, 5-dimethoxycanthin-6-one group. The expression of Caspase1 in glioblastoma cells treated with 4, 5-dimethoxycanthin-6-one increased, and the number of apoptotic cells increased. The tumor volume of mice injected with 4, 5-dimethoxycanthin-6-one decreased significantly. CONCLUSION: 4, 5-Dimethoxycanthin-6-one could act as a novel inhibitor of LSD1 to regulate glioblastoma, which could inhibit the proliferation of U251 and T98G cells and induce their apoptosis and pyroptosis. It is a potential drug for the treatment of glioblastoma.

Characterization of cadmium accumulation mechanism between eggplant (Solanum melongena L.) cultivars.

Excessive cadmium (Cd) accumulation in vegetables due to farmland pollution constitutes a serious threat to human health. Eggplant has a tendency to accumulate Cd. To investigate the mechanism of the differences in Cd accumulation levels between high-Cd (BXGZ) and low-Cd (MYQZ) eggplant cultivar, physiological and biochemical indicators and mRNA expression of eggplant were examined using photosynthetic apparatus, biochemical test kits, Fourier transform infrared (FTIR) spectroscopy and transcriptome sequencing, etc. The results of biochemical test kits and FTIR revealed that MYQZ enhanced pectin methylesterase (PME) activity, and lignin and pectin content in the root cell wall, which was associated with the upregulation of PME, cinnamyl-alcohol dehydrogenase and peroxidase (PODs). Higher levels of cysteine and glutathione (GSH) contents and upregulation of genes associated with sulfur metabolism, as well as higher expression of ATP-binding cassette transporters (ABCs), cation exchangers (CAX) and metal tolerance proteins (MTPs) were observed in MYQZ. In BXGZ, the higher stomatal density and stomatal aperture as well as higher levels of Ca2+ binding protein-1 (PCaP1) and aquaporins and lower levels of A2-type cyclins (CYCA2-1) are consistent with an enhanced transpiration rate in BXGZ. Furthermore, a more developed root system was shown to be associated with higher levels of auxin response factor (ARF19), GATA transcription factors (GATA4, 5 and 11) and auxin efflux carrier component (PIN5) in BXGZ. In conclusion, highly active PME, and higher levels of lignin and pectin in MYQZ are expected to reduce Cd toxicity, while Cd translocation can be inhibited with the help of ABC and other Cd transporters. As for BXGZ, the uptake and translocation of Cd were enhanced by the developed root system and stronger transpiration.

Biomimetic Ceramic Composite: Characterization, Cell Response, and In Vivo Biocompatibility.

The present study aimed to synthesize biphasic calcium phosphate ceramics (CaPs) composed of ß-tricalcium phosphate (ß-TCP) and hydroxyapatite (HAp) from the propagated Scleractinian coral and dicalcium phosphate anhydrous using a solid-state reaction followed by heat treatment at a temperature of 1100 °C for 1 h to 7 days. The as-prepared coral and coral-derived biphasic CaPs samples were characterized through scanning electron microscopy, X-ray diffractometry, Fourier transform infrared spectroscopy, and Raman spectroscopy. The cell response of the biphasic CaPs was evaluated by in vitro cytotoxicity assessment using mouse fibroblast (L929) cells. The bilateral femoral defect rabbit model was used to assess the early local reaction of the coral-derived biphasic CaPs bone graft on tissue. The results confirmed that the co-existence of ß-TCP and HAp was formed at 1100 °C for 1 h. The ratio of HA/ß-TCP increased as the heat-treatment time increased. The coral-derived biphasic CaPs comprising 61% HAp and 39% ß-TCP (defined as HT-3) were not cytotoxic. Furthermore, no significant differences in local tissue reaction were observed between the HT-3 sample and autogenous bone. Therefore, the synthesized coral-derived biphasic CaPs is a candidate for bone grafting due to its good biocompatibility.

Molecular and biochemical mechanisms underlying boron-induced alleviation of cadmium toxicity in rice seedlings.

Both cadmium (Cd) contamination and boron (B) deficiency in farmland soils pose a threat to the yield and quality of crops in Southern China. The present study investigated the mechanisms by which B reduces Cd accumulation in rice (Oryza sativa) seedlings. Boron supplementation partially restored the decline in shoot and root biomass caused by Cd treatment (26% and 33%, respectively), with no significant difference between the B+Cd and control groups. We also found that B significantly reduced shoot and root Cd concentrations (by 64% and 25%, respectively) but increased Cd concentration (by 43%) and proportion (from 38% to 55%) in root cell walls. Transcriptome analysis and biochemical tests suggested that B supplementation enhanced lignin and pectin biosynthesis, pectin demethylation, and sulfur and glutathione metabolism. Moreover, B decreased the expression of some Cd-induced transporter-related genes (i.e., HMA2, Nramp1, and several ABC genes). These results indicate that B relieved Cd toxicity and reduced Cd accumulation in rice seedlings by restraining Cd uptake and translocation from root to shoot by improving Cd tolerance and chelation ability. These novel findings would benefit further investigations into how B influences Cd uptake, translocation, detoxification, and accumulation in crops.