Hemin mitigates contrast-induced nephropathy by inhibiting ferroptosis via HO-1/Nrf2/GPX4 pathway.

Contrast-induced nephropathy (CIN) is a common complication with adverse outcome after iodinated-contrast injection, yet still lacking effective medication. Heme oxygenase-1 (HO-1) has been reported to play an important role against renal injuries. Hemin, a HO-1 inducer and anti-porphyria medicine, may have a promising effect against CIN. In this study, we aim to investigate the effect of hemin on CIN model and the underlying molecular mechanisms in human proximal tubule epithelial cells (HK-2). To mimic a common condition in percutaneous coronary intervention (PCI) patients, CIN was induced by intravenous iopromide in high-fat fed diabetic rats. We found hemin, given right before iopromide, mitigated CIN with enhanced antioxidative capacity and reduced oxidative stress. HK-2 cells insulted by iopromide demonstrated decreased cell vitality and rising reactive oxygen species (ROS), which could also be inhibited by hemin. The effects of hemin involved a key molecule in ferroptosis, glutathione peroxidase (GPX4), whose down-expression by small interfering RNA (siRNA) reversed the effect of hemin on HK-2 cells. Furthermore, hemin's induction of GPX4 involved HO-1 and nuclear factor erythroid 2-related factor 2 (Nrf2). Either HO-1 or Nrf2 inhibitor prevented hemin's effect on GPX4 to a comparable extent, and over-expression of Nrf2 increased GPX4 expression. Moreover, intervention of ferroptosis inhibitor liproxstatin-1 also alleviated CIN in vivo. Therefore, we showed hemin mitigated CIN, inhibiting oxidative stress and ferroptosis, by upregulation of GPX4 via activation of HO-1/Nrf2. Hemin, as a clinical medicine, has a translational significance in treating CIN, and anti-ferroptosis is a potential therapeutic strategy for CIN.

Targeted Therapy with Anlotinib for a Patient with an Oncogenic FGFR3-TACC3 Fusion and Recurrent Glioblastoma.

We describe a case of recurrent glioblastoma treated with anlotinib in this report. The patient was administered anlotinib 12 mg p.o. once every day (days 1-14, with a 21-day cycle) (anlotinib clinical study NCT04004975) and oral temozolomide chemotherapy 100 mg/m2 (days 1-7, days 15-21, 28-day cycle; 12 cycles). After 2 months of therapy, the patient achieved a partial response that has been maintained for >17 months of follow-up. Molecular characterization confirmed the presence of a TERT promoter mutation, wild-type IDH1/2, an FGFR3-TACC3 fusion, and FGFR3 amplification in the patient. Anlotinib is a multitarget tyrosine kinase inhibitor that was originally designed to inhibit VEGFR2/3, FGFR1-4, PDGFRα/ß, and c-Kit. Patients with TERT promoter mutations and high-grade IDH-wild-type glioma have shorter overall survival than patients with IDH-wild-type glioma without TERT promoter mutations. However, this patient had a favorable clinic outcome, and FGFR3-TACC3 fusion may be a new marker for treatment of glioma with anlotinib. KEY POINTS: This case study is believed to be the first report that FGFR3-TACC3 fusion could be a novel indication to treat recurrent glioblastoma with the drug anlotinib. This case exhibited an exceptional response (maintained partial response >17 months) after 2-month combined therapy of anlotinib and oral temozolomide chemotherapy. This case also underscores the importance of molecular diagnosis for clinically complex cases. Tumor tissue-based assessment of molecular biomarkers in brain tumors has been successfully translated into clinical application.

Complete genome sequence of Mycobacterium Mya-zh01, an endophytic bacterium, promotes plant growth and seed germination isolated from flower stalk of Doritaenopsis.

No genomic sequence of Mycobacterium isolated from orchids has been reported yet; therefore, this study intends to analyze the complete genomic sequence of a growth-promoting Mycobacterium from orchid Doritaenopsis. Mycobacterium strain Mya-zh01 was isolated from the flower stalk of Doritaenopsis Jiuhbao Red Rose. Our results show that Mya-zh01 can effectively produce and secrete the plant growth hormone indole-3-acetic acid (IAA). Inoculation of Mya-zh01 increased root number and length, plant height, leaf number, and leaf length in Doritaenopsis. Furthermore, inoculation of Mya-zh01 promotes seed germination in Doritaenopsis. We sequenced and assembled chromosome for Mya-zh01 (5,027,704 bp with 68.48% GC content), which was predicted to encode 4968 proteins with functions in oxidation reduction, growth, plasma membrane, ATP and DNA binding, carbon metabolism and biosynthesis of amino acids pathways. Mya-zh01 may trap iron from nature or host cells to facilitate the growth of the orchids by producing two siderophores (Mycobactin and Nocobactin NA). Four pathways (tryptamine, indole-3-acetamide, indole-3-pyruvate, and flavin monooxygenase) and seven enzymes [tryptophan synthase alpha chain, tryptophan synthase beta chain, amidase, monoamine oxidase, indole-3-pyruvate monooxygenase, indole-3-pyruvate decarboxylase and aldehyde dehydrogenase (NAD +)] involved in IAA biosynthesis were predicted in Mya-zh01 genome. In conclusion, this study demonstrated the significance of Mya-zh01 in facilitating plant growth and seed germination in Doritaenopsis by IAA biosynthesis, which provides a new insight into the mechanism of plant-bacteria interaction in Doritaenopsis.

Quantifying Variation in Soybean Due to Flood Using a Low-Cost 3D Imaging System.

Flood has an important effect on plant growth by affecting their physiologic and biochemical properties. Soybean is one of the main cultivated crops in the world and the United States is one of the largest soybean producers. However, soybean plant is sensitive to flood stress that may cause slow growth, low yield, small crop production and result in significant economic loss. Therefore, it is critical to develop soybean cultivars that are tolerant to flood. One of the current bottlenecks in developing new crop cultivars is slow and inaccurate plant phenotyping that limits the genetic gain. This study aimed to develop a low-cost 3D imaging system to quantify the variation in the growth and biomass of soybean due to flood at its early growth stages. Two cultivars of soybeans, i.e. flood tolerant and flood sensitive, were planted in plant pots in a controlled greenhouse. A low-cost 3D imaging system was developed to take measurements of plant architecture including plant height, plant canopy width, petiole length, and petiole angle. It was found that the measurement error of the 3D imaging system was 5.8% in length and 5.0% in angle, which was sufficiently accurate and useful in plant phenotyping. Collected data were used to monitor the development of soybean after flood treatment. Dry biomass of soybean plant was measured at the end of the vegetative stage (two months after emergence). Results show that four groups had a significant difference in plant height, plant canopy width, petiole length, and petiole angle. Flood stress at early stages of soybean accelerated the growth of the flood-resistant plants in height and the petiole angle, however, restrained the development in plant canopy width and the petiole length of flood-sensitive plants. The dry biomass of flood-sensitive plants was near two to three times lower than that of resistant plants at the end of the vegetative stage. The results indicate that the developed low-cost 3D imaging system has the potential for accurate measurements in plant architecture and dry biomass that may be used to improve the accuracy of plant phenotyping.

Genome Evolution Analysis of Recurrent Testicular Malignant Mesothelioma by Whole-Genome Sequencing.

BACKGROUND/AIMS: Malignant mesothelioma of the tunica vaginalis testis is a rare and lethal disease. The genomic characteristics and genetic changes of tumor cells during the progression of this disease are unknown. METHODS: we performed whole-genome sequencing of four successive tumor samples derived from surgery and a blood sample in a single patient. RESULTS: All tumors were found to have significant C-to-T and T-to-C mutations, and amplification of copy number in chromosomes 1 and 12 were notified in all tumor samples. Subclone analysis revealed a parallel evolution of the tumor in this patient. We also identified some mutations in mesothelioma-associated genes such as KIF25, AHNAK, and PRDM2. CONCLUSIONS: The results showed a comprehensive genomic change in malignant mesothelioma of the tunica vaginalis testis and provide a better understanding of the clonal evolution during tumor recurrence and metastasis.

Adjustable single-incision mini-slings (Ajust®) versus other slings in surgical management of female stress urinary incontinence: a meta-analysis of effectiveness and complications.

BACKGROUND: Adjustable single-incision mini-sling (SIMS) is a new category of SIMS for stress urinary incontinence (SUI). The aim of this study was to compare the efficacy and safety of adjustable single-incision mini-sling with other slings. METHODS: Literature search in databases such as Pubmed, and Conchrane Library was performed up to December, 2015. The outcomes including cure rate, operation time, postoperative pain score and complications were reanalyzed. The pooled relative risk (RR) and mean difference (MD) with their 95% confidence interval (95% CI) were calculated by RevMan v5.0. RESULTS: Eight studies with 1093 SUI female patients were included. There was no significant difference between adjustable SIMS and other slings (transobturator slings and MiniArc) in patients subjective cure rate and objective cure rate. In addition, adjustable SIMS was associated with a significantly shorter operative time and lower postoperative pain score when comparing adjustable SIMS with transobturator tape (MD = - 1.35; 95%CI: -2.24 to - 0.46, P = 0.003). For the complications, there was also no significant difference between adjustable SIMS and transobturator slings. CONCLUSIONS: Adjustable SIMS had equally efficacy for SUI compared with transobturator slings and MiniArc. However, the significantly shorter operative time and lower postoperative pain score than transobturator tape supported the clinical application of adjustable SIMS.

Hypoxia-induced autophagy promotes human prostate stromal cells survival and ER-stress.

Benign prostatic hyperplasia (BPH) is emerging as one of the most common diseases seriously threatening the health of elderly men. Accumulating evidences indicate that hypoxia could induce BPH. However, the underlying mechanism of BPH induced by hypoxia is not clear. In the study, hypoxia-induced autophagy could promote cell survival and endoplasmic reticula stress (ER stress) in WPMY-1 cells. Cell viability induced by hypoxia could been decreased by autophagy inhibitors (3-methyladenine, bafilomycin A1) or siRNA interference in two autophagy genes (Beclin1, ATG5) in WPMY-1 cells. Furthermore, ER stress was present in hypoxia-treated WPMY-1 cells, while autophagy and cell survival could been inhibited by C/EBP-homologous protein siRNA (CHOP), which is an important protein of ER stress pathway. Taken together, our data support a novel model that autophagy as a cytoprotective response promotes cell survival via ER stress under hypoxia in human prostate stromal cells.

Secretory breast carcinoma in a 41-year-old man with long-term follow-up: a special report.

Secretory breast carcinoma (SBC) is a rare tumor that is particularly rare in male adults. To our knowledge, only 28 previous male cases of secretory breast carcinoma have been reported. The present a case of secretory breast carcinoma has the longest symptom duration of (40 years) in a male individual until now. Typically, the clinical features and treatment of male SBC are similar with female SBC. The ETV6-NTRK3 fusion gene is a specific genetic alteration in SBC. When compared to other types of male breast cancer, patients with male secretory breast cancer are much younger, and have a lower rate of estrogen/progesterone hormone receptor positivity. Modified radical mastectomy has been favored as a therapeutic approach in all female SBC, male SBC and other types of male breast cancer. [corrected].

The Puerarin improves renal function in STZ-induced diabetic rats by attenuating eNOS expression.

Diabetic nephropathy (DN) is a serious complication and it leads to kidney failure. The endothelial nitric oxide synthases (eNOS) seems to be involved in the development and progression of DN. The Puerarin is a well-known Chinese traditional formula, which is widely used in clinical practice for the treatment of kidney disease. The present study was designed to investigate the renal protective effects of Puerarin on streptozotocin (STZ)-induced diabetic rats. Thirty Sprague-Dawley (SD) male rats were divided into three groups at random. The diabetic group and the Puerarin-treated group were intraperitoneally injected with STZ 65 mg/kg and the Puerarin-treated rats were intraperitoneally injected Puerarin 100 mg/kg/day for 4 weeks. The results showed the Puerarin could improve body weight, blood sugar, BUN and SCr levels, and reduce ultrastructural changes of kidney in diabetic rats. It also attenuated eNOS expression in glomerular endothelial cells and tubular cells of diabetic rats with Puerarin treatment (p < 0.05). The Puerarin had significant renal-protective effects for the diabetic nephropathy, possibly through regulating eNOS expression, and it may be used as a potential therapeutic reagent.

Resistance training combined with ß-hydroxy ß-methylbutyrate for patients with critical illness: A four-arm, mixed-methods, feasibility randomised controlled trial.

OBJECTIVES: This study aimed to assess the feasibility, safety, acceptability, and potential effectiveness of resistance training (RT) with or without ß-Hydroxy ß-Methylbutyrate (HMB) intervention program for ICU patients. DESIGN: Open-label, parallel group, mixed method, randomized controlled trial. SETTINGS: A tertiary general hospital in Fuzhou, China. METHODS: Participants were randomly allocated to one of four groups. The RT group received supervised multilevel resistance training (RT) using elastic bands, administered by trained ICU nurses. The HMB group received an additional daily dose of 3.0 g HMB. The combination group underwent both interventions concurrently, while the control group received standard care. These interventions were implemented throughout the entire hospitalization period. Primary outcomes included feasibility indicators such as recruitment rate, enrollment rate, retention rate, and compliance rate. Secondary outcomes covered adverse events, acceptability (evaluated through questionnaires and qualitative interviews), and physical function. Quantitative analysis utilized a generalized estimation equation model, while qualitative analysis employed directed content analysis. RESULTS: All feasibility indicators met predetermined criteria. Forty-eight patients were randomly assigned across four arms, achieving a 96% enrollment rate. Most patients adhered to the intervention until discharge, resulting in a 97.9% retention rate. Compliance rates for both RT and HMB interventions approached or exceeded 85%. No adverse events were reported. The intervention achieved 100% acceptability, with a prevailing expression of positive experiences and perception of appropriateness. The RT intervention shows potential improvement in physical function, while HMB does not. CONCLUSIONS: Implementing nurse-led resistance training with elastic bands with or without HMB proved to be feasible and safe for ICU patients. IMPLICATIONS FOR CLINICAL PRACTICE: A large-scale, multicenter clinical trials are imperative to definitively assess the impact of this intervention on functional outcomes in this population.

Combining Traditional Chinese Herbs and csDMARDs for the Treatment of Rheumatoid Arthritis Involves Tapering and Discontinuing Glucocorticoids: Protocol for a Two-Stage Non-Randomized Controlled Trial.

Glucocorticoids (GC) are crucial in the treatment of rheumatoid arthritis (RA), but discontinuing GC effectively in RA patients poses a significant challenge for rheumatologists. In this two-stage, single-center, non-randomized controlled trial, we investigated the benefits of combining Chinese traditional herbal treatment with csDMARDs to aid GC discontinuation in terms of GC tapering, disease control, and safety. A total of 231 participants were enrolled, of which 150 eligible subjects were included in the first phase and allocated to three groups (control group, treatment group 1, and treatment group 2) based on their willingness to take traditional Chinese medicine and syndrome differentiation, in a 1:1:1 ratio. All groups received basic treatment consisting of methotrexate tablets (10 mg, qw), leflunomide (10 mg, qd), and stratified GC bridging therapy and tapering regimen (The intervention regimen was developed based on rigorous adherence to available evidence). Treatment group 1 received basic treatment combined with Juanbi Granule, while treatment group 2 received basic treatment combined with Yupingfeng Guizhi Decoction Granule. Efficacy was evaluated after a 12-week follow-up, with slightly adjustments to the treatment group based on efficacy and change of syndrome, followed by continued observation until 24 weeks to complete the study. The efficacy evaluation and data analysis were conducted in a blinded manner, including group label concealment, data cleaning, confounder and control regimen analysis, and outcome analysis. This project has received ethical approval from the Ethics Committee of Yunnan Provincial Hospital of Traditional Chinese Medicine (YLZ [2022] Ethical Review No. (006)-01) and has been registered with the China Clinical Trials Registry (Registration number: ChiCTR2300067676, Registered 17 January 2023, https://www.chictr.org.cn/showproj.html?proj=184908). This trial was the first to evaluate the clinical efficacy of combining Chinese herbal medicines with standard Western medicines to facilitate the discontinuation of glucocorticoid (GC) therapy in patients with rheumatoid arthritis (RA).

A single-arm, multicenter, phase 2 clinical study of recombinant humanized anti-HER2 monoclonal antibody-MMAE conjugate (MRG002) in HER2-positive unresectable locally advanced or metastatic urothelial carcinoma.

BACKGROUND: MRG002 is a novel HER2-targeted antibody-drug conjugate being investigated in the MRG002-006 trial to evaluate the efficacy and safety in HER2-positive urothelial carcinoma patients. METHODS: This is an open-label, single-arm, multicenter phase II study. Eligibility criteria included: histologically confirmed HER2 IHC 2 + or 3 + UC, prior received ≥ 1 standard treatment. Patients in this study received MRG002 every 3 weeks until progressive disease or unacceptable toxicity. The primary endpoint was confirmed ORR per RECIST 1.1. RESULTS: As of February 24, 2023, a total of 43 patients were enrolled. The median age was 60. 9 patients were dosed at 2.6 mg/kg and 34 patients were dosed at 2.2 mg/kg. At baseline, most patients (29/43) received ≥ 2 lines of treatment and 35 (81.4%) patients had prior ICI therapy. FISH test was performed in 41 patients and 9 (22.0%) were positive. By the cut-off date, 41 patients were evaluable and the ORR was 53% (95%CI：38.9%-67.5%), with 6.9% CR, and the DCR was 83.7% (95%CI：70.0%-91.9%). The median PFS and OS for the 43 patients were 7.0 months (95%CI：5.4-NE) and 14.9 months (95%CI：11.9-NE), respectively. The ORR was 77.8% in 9 patients with positive HER2 FISH results. Most common treatment-related AEs were anemia (51.2%), alopecia (44.2%) and neutropenia (39.5%); most were grade 1 or 2. CONCLUSION: Preliminary results of MRG002 demonstrated a clinically meaningful response in pretreated HER-2 positive unresectable locally advanced or metastatic UC patients. MRG002 at 2.2 mg/kg was well tolerated with a manageable toxicity.

In vitro antifungal drug susceptibilities of Penicillium marneffei from China.

Penicillium marneffei infections in immunocompromised patients are often fatal, but early treatment with appropriate antifungal agents may have a good prognosis. To select drugs for treating P. marneffei infection in Southern China, the susceptibilities of antifungal agents against P. marneffei isolates were evaluated. Twenty-five strains of P. marneffei were isolated from patients from 2008 to 2010 in Guangxi Province of China, and 14 strains were isolated from bamboo rats. The activity of voriconazole, fluconazole, itraconazole, terbinafine, and amphotericin B on the isolates was assessed by MIC analysis. Voriconazole MIC against strains of P. marneffei ranged from 0.004 to 0.25 mg/l, and it had the lowest MIC (geometric mean values, 0.04 mg/l) in comparison to the other antifungal agents. The MICs of other antifungal agents, in order of lowest to highest, were as follows: itraconazole, terbinafine, amphotericin B, and fluconazole. The results show voriconazole and itraconazole are active against P. marneffei isolates in vitro, and terbinafine may have unrealized usefulness in the treatment of infections caused by this yeast form.

CENPE and LDHA were potential prognostic biomarkers of chromophobe renal cell carcinoma.

BACKGROUND: Most sarcomatoid differentiated renal cell carcinoma was differentiated from Chromophobe renal cell carcinoma (KICH) and related to a bad prognosis. Thus, finding biomarkers is important for the therapy of KICH. METHODS: The UCSC was used for determining the expression of mRNA and miRNA and clinical data in KICH and normal samples. KEGG and GO were used for predicting potential function of differently expressed genes (DEGs). Optimal prognostic markers were determined by Lasso regression. Kaplan-Meier survival, ROC, and cox regression were used for assessing prognosis value. GSEA was used for predicting potential function of markers. The relations between markers and immune cell infiltration were determined by Pearson method. The upstream miRNA of markers was predicted in TargetScan and DIANA. RESULTS: The 6162 upregulated and 13,903 downregulated DEGs were identified in KICH. Further CENPE and LDHA were screened out as optimal prognostic risk signatures. CENPE was highly expressed while LDHA was lowly expressed in KICH samples, and the high expressions of 2 genes contributed to bad prognosis. The functions of CENPE and LDHA were mainly enriched in proliferation related pathways such as cell cycle and DNA replication. In addition, the correlation of 2 genes with immune infiltrates in KICH was also observed. Finally, we found that has-miR-577 was the common upstream of 2 genes and the binding sites can be predicted. CONCLUSION: CENPE and LDHA were identified as the important prognostic biomarkers in KICH, and they might be involved in the proliferation of cancer cell.

Androgen deprivation induces bladder histological abnormalities and dysfunction via TGF-ß in orchiectomized mature rats.

Symptomatic late-onset hypogonadism, one of the most common elder diseases, is defined as a syndrome associated with a deficiency in serum testosterone. Recent studies have indicated that androgen deficiency in men is also associated with lower urinary tract symptoms and bladder dysfunction. To determine the pathologic consequences of androgen deprivation in bladder histology and function, we addressed the underlying mechanism. Male rats were divided into 4 groups: emasculated rats (EMR), emasculated rats treated with testosterone, emasculated rats treated with anti- transforming growth factor-ß (TGF-ß) neutralizing antibody, and sham surgery rats. TGF-ß is a common profibrotic factor that mediates the pathologic process of fibrosis in multiple organs. Two months later, urodynamic evaluations were employed to determine the bladder function in vivo. And then rats were sacrificed, and the bladder tissues were collected. Histological studies were employed to determine the degree of bladder fibrosis. Real time PCR was used to evaluate the mRNA level of pro-collagen I, a fibrotic marker. We demonstrate here that androgen deficiency induces bladder fibrosis and decreases the bladder maximal volume and compliance. Androgen replacement treatment completely prevented the histological and functional abnormalities induced by androgen deficiency. Subsequently, we identified that androgen deprivation induced the induction of TGF-ß mRNA level. Importantly, treatment with anti-TGF-ß antibody abolished androgen deprivation-induced bladder fibrosis and dysfunction. Our study reveals an essential role of TGF-ß in the pathogenesis of androgen deprivation-induced bladder fibrosis and dysfunction and offers a potential target for prevention and treatment of bladder dysfunction associated with androgen deficiency.

Effects of Process Parameters on the Corrosion Resistance and Biocompatibility of Ti6Al4V Parts Fabricated by Selective Laser Melting.

Excellent biocompatibility and corrosion resistance of implants are essential for Ti6Al4V parts fabricated by selective laser melting (SLM) for biomedical applications. To achieve better corrosion resistance and biocompatibility of Ti6Al4V parts, the effects of SLM processing parameters on the corrosion resistance and the biocompatibility of Ti6Al4V parts are investigated by changing the scanning speeds and laser powers. The detailed influence mechanism of processing parameters on the properties of Ti6Al4V parts is studied from two aspects, including microstructure and defects. It is found that the corrosion resistance and biocompatibility of Ti6Al4V parts can be adjusted by changing the scanning speed and the laser power due to the constituent phase and the number and size of defect holes of Ti6Al4V parts. Compared with the laser power, the scanning speed has a stronger influence on the performance of the part, which can be used as "coarse tuning" based on the performance requirements. At the scanning speed of 1100 mm/s and the laser power of 280 W, Ti6Al4V parts with better corrosion resistance can be obtained. Ti6Al4V parts with better biocompatibility are fabricated at the scanning speed of 1200 mm/s and the laser power of 200 W.

Micro/Nanoarchitectonics of 3D Printed Scaffolds with Excellent Biocompatibility Prepared Using Femtosecond Laser Two-Photon Polymerization for Tissue Engineering Applications.

The fabrication of high-precision scaffolds with excellent biocompatibility for tissue engineering has become a research hotspot. Two-photon polymerization (TPP) can break the optical diffraction limit and is used to fabricate high-resolution three-dimensional (3D) microstructures. In this study, the biological properties, and machinability of photosensitive gelatin methacrylate (GelMA) hydrogel solutions are investigated, and the biocompatibility of 3D scaffolds using a photosensitive GelMA hydrogel solution fabricated by TPP is also evaluated. The biological properties of photosensitive GelMA hydrogel solutions are evaluated by analyzing their cytotoxicity, swelling ratio, and degradation ratio. The experimental results indicate that: (1) photosensitive GelMA hydrogel solutions with remarkable biological properties and processability are suitable for cell attachment. (2) a micro/nano 3D printed scaffold with good biocompatibility is fabricated using a laser scanning speed of 150 µm/s, laser power of 7.8 mW, layer distance of 150 nm and a photosensitive GelMA hydrogel solution with a concentration of 12% (w/v). Micro/nano additive manufacturing will have broad application prospects in the tissue engineering field.

Material Extrusion Based Fabrication of Surgical Implant Template and Accuracy Analysis.

An implant template with great precision is significantly critical for clinical application. Currently, the application of an immediate implant remains limited by the deviations between the planned and actual achieved positions and long periods required for preparation of implant templates. Material Extrusion (MEX), as one kind of 3D printing method, is well known for its low cost and easy operation. However, the accuracy of the implant template printed by MEX has not been fully researched. To investigate the accuracy and feasibility of in vitro computer-guided surgery assisted with a MEX printed template, unidentified plaster samples missing a maxillary molar are digitalized. Mimics software (Materialise, Leuven, Belgium) is used for preoperative design. Surgical templates are fabricated by a MEX 3D printer (Lingtong III, Beijing SHINO, Beijing, China). Postoperative CBCT data are obtained after surgical template placement. The differences in positions of X, Y, Z, and dXYZ as well as angulations between the placed and the designed template are measured on labiolingual and mesiodistal planes. The deviations of the planned and the actual outcome in each dimension are observed and analyzed. Data from different samples indicate that the mean deviation of the angle measures approximately 3.640°. For position deviation, the maximum deviation is found in the z-direction and the mean deviation is about 0.365 ± 0.136 mm. The mean deviation of space Euclidean distance dXYZ is approximately 0.537 ± 0.123 mm. Implant templates fabricated by MEX present a relatively high accuracy for tooth-supported guide implantation.

LncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of bone marrow-derived mesenchymal stem cells by targeting miR-150-5p.

Osteoporosis (OP) is a systemic bone metabolic disease with complicated pathogenesis and is difficult to cure clinically. The regulatory mechanisms of OP are needed to be further investigated. In the present study, we focused on the role of myocardial infarction-associated transcript (MIAT) in OP development and examined the underlying mechanism. The serum expression levels of MIAT in samples from patients with OP and healthy controls were compared using quantitative reverse transcription-PCR (qRT-PCR). The dual-luciferase reporter assay was used to confirm the relationship between MIAT and its potential target microRNA, i.e., miR-150-5p. Moreover, bone marrow-derived mesenchymal stem cells (BMSCs) were cultured and transfected with MIAT shRNA, with or without miR-150-5p inhibitor. EdU staining and colony formation analysis were performed to determine the proliferation ability of these cells. Furthermore, the TUNEL assay and flow cytometry were used to assess BMSC apoptosis. Finally, RT-PCR and Western blot assays were employed to assess the expression of osteogenic differentiation biomarkers. Compared with controls, the expression of MIAT was significantly increased, whereas that of miR-150-5p was markedly decreased in patients with OP. MIAT and miR-150-5p expression levels exhibited a strong negative correlation. Furthermore, osteogenic differentiation indicators were suppressed in serum of OP patients. MIAT was downregulated, and miR-150-5p was upregulated in induced to osteogenic differentiation BMSCs. Furthermore, downregulation of MIAT dramatically promoted osteogenic differentiation, increased proliferation, and inhibited apoptosis in BMSCs; miR-150-5p inhibitor abrogated the effects of MIAT. In conclusion, lncRNA MIAT can regulate the proliferation, apoptosis, and osteogenic differentiation of BMSCs.

Circ_0014359 promotes oral squamous cell carcinoma progression by sponging miR-149.

This study aimed to explore the role and mechanism of circ_0014359 in the OSCC. We firstly investigated the expression levels of circ_0014359 in OSCC tissues and cell lines. Then, the effects of knocking down circ_0014359 on cellular viability, apoptosis, migration, and invasion of OSCC cell lines were observed by cell counting kit-8 assay, flow cytometry, and transwell assay. Xenografts mouse model was established to explore the in vivo effect of circ_0014359 on the tumor volume and size of OSCC. We found that circ_0014359 was highly expressed in the OSCC tissues and cell lines compared to the normal controls (P<0.05). The expression of circ_0014359 was associated with the survival of patients (P<0.05). For the OSCC cell lines, circ_0014359 knock down induced apoptosis and inhibited migration, invasion, and epithelial-mesenchymal transition of OSCC cells (P<0.001). In vivo, silencing the circ_0014359 blocked the growth of OSCC tumors. The circ_0014359 can directly interact with the micro-RNA-149 (miR-149). Inhibition of miR-149 can rescue the inhibitory effects of circ_0014359 knock down on OSCC cells. The circ_0014359-miR-149 pathway may be a novel target for developing strategies for the diagnosis and treatment of OSCC.