From everyday life to measurable problematic smartphone use: The development and validation of the Smartphone Use Problems Identification Questionnaire (SUPIQ).

Background and aims: Problematic smartphone use (PSU) has gained attention, but its definition remains debated. This study aimed to develop and validate a new scale measuring PSU-the Smartphone Use Problems Identification Questionnaire (SUPIQ). Methods: Using two separate samples, a university community sample (N = 292) and a general population sample (N = 397), we investigated: (1) the construct validity of the SUPIQ through exploratory and confirmatory factor analyses; (2) the convergent validity of the SUPIQ with correlation analyses and the visualized partial correlation network analyses; (3) the psychometric equivalence of the SUPIQ across two samples through multigroup confirmatory factor analyses; (4) the explanatory power of the SUPIQ over the Short Version of Smartphone Addiction Scale (SAS-SV) with hierarchical multiple regressions. Results: The results showed that the SUPIQ included 26 items and 7 factors (i.e., Craving, Coping, Habitual Use, Social Conflicts, Risky Use, Withdrawal, and Tolerance), with good construct and convergent validity. The configural measurement invariance across samples was established. The SUPIQ also explained more variances in mental health problems than the SAS-SV. Discussion and conclusions: The findings suggest that the SUPIQ shows promise as a tool for assessing PSU. Further research is needed to enhance and refine the SUPIQ as well as to investigate its clinical utility.

A novel tsRNA-5008a promotes ferroptosis in cardiomyocytes that causes atrial structural remodeling predisposed to atrial fibrillation.

Atrial fibrillation (AF) is an extremely common clinical arrhythmia disease, but whether its mechanism is associated with ferroptosis remains unclear. The tRNA-derived small RNAs (tsRNAs) are involved in a variety of cardiovascular diseases, however, their role and mechanism in atrial remodeling in AF have not been studied. We aimed to explore whether tsRNAs mediate ferroptosis in AF progression. The AF models were constructed to detect ferroptosis-related indicators, and Ferrostatin-1 (Fer-1) was introduced to clarify the relationship between ferroptosis and AF. Atrial myocardial tissue was used for small RNA sequencing to screen potential tsRNAs. tsRNA functioned on ferroptosis and AF was explored. Atrial fibrosis and changes in the cellular structures and arrangement were observed in AF mice model, and these alterations were accompanied by ferroptosis occurrence, exhibited by the accumulation of Fe2+ and MDA levels and the decrease of expression of FTH1, GPX4, and SLC7A11. Blocking above ferroptosis activation with Fer-1 resulted in a significant improvement for AF. A total of 7 tsRNAs were upregulated (including tsRNA-5008a) and 2 tsRNAs were downregulated in atrial myocardial tissue in the AF group compared with the sham group. We constructed a tsRNA-mRNA regulated network, which showed tsRNA-5008a targeted 16 ferroptosis-related genes. Knockdown of tsRNA-5008a significantly suppressed ferroptosis through targeting SLC7A11 and diminished myocardial fibrosis both in vitro and in vivo. On the contrary, tsRNA-5008a mimics promoted ferroptosis in cardiomyocytes. Collectively, tsRNA-5008a involved in AF through ferroptosis. Our study provides novel insights into the role of tsRNA-5008a mediated ferroptosis in AF progression.

Case series of ovarian neuroendocrine carcinoma: overview of clinicopathological features.

BACKGROUND: Ovarian neuroendocrine carcinoma (O-NEC) is a relatively uncommon neoplasm, and the current knowledge regarding its diagnosis and management is limited. In this series, our objective was to provide an overview of the clinicopathological characteristics of the disease by analyzing clinical case data to establish a theoretical foundation for the diagnosis and management of O-NEC. CASE PRESENTATION: We included three patients in the present case series, all of whom were diagnosed with primary O-NEC based on pathomorphological observation and immunohistochemistry. Patient 1 was a 62-year-old patient diagnosed with small cell carcinoma (SCC) of the pulmonary type. Post-surgery, the patient was diagnosed with stage II SCC of the ovary and underwent standardized chemotherapy; however, imaging examinations conducted at the 16-month follow-up revealed the existence of lymph node metastasis. Unfortunately, she passed away 21 months after the surgery. The other two patients were diagnosed with carcinoid tumors, one at age 39 and the other at age 71. Post-surgery, patient 2 was diagnosed with a carcinoid in the left ovary, whereas patient 3 was diagnosed with a carcinoid in her right ovary based on clinical evaluation. Neither of the cases received adjuvant therapy following surgery; however, they have both survived for 9 and 10 years, respectively, as of date. CONCLUSION: Primary O-NECs are rare and of diverse histological types, each of which has its own unique biological features and prognosis. SCC is a neoplasm characterized by high malignancy and a poor prognosis, whereas carcinoid tumors are of lesser malignancy and have a more favorable prognosis.

Substrate-dependent interaction of SPOP and RACK1 aggravates cardiac fibrosis following myocardial infarction.

Speckle-type pox virus and zinc finger (POZ) protein (SPOP), a substrate recognition adaptor of cullin-3 (CUL3)/RING-type E3 ligase complex, is investigated for its role in cardiac fibrosis in our study. Cardiac fibroblasts (CFs) activation was achieved with TGF-ß1 (20 ng/mL) and MI mouse model was established by ligation of the left anterior descending coronary, and lentivirus was employed to mediate interference of SPOP expression. SPOP was increased both in fibrotic post-MI mouse hearts and TGF-ß1-treated CFs. The gain-of-function of SPOP promoted myofibroblast transformation in CFs, and exacerbated cardiac fibrosis and cardiac dysfunction in MI mice, while the loss-of-function of SPOP exhibited the opposite effects. Mechanistically, SPOP bound to the receptor of activated protein C kinase 1 (RACK1) and induced its ubiquitination and degradation by recognizing Ser/Thr-rich motifs on RACK1, leading to Smad3-mediated activation of CFs. Forced RACK1 expression canceled the effects of SPOP on cardiac fibrosis. The study reveals therapeutic targets for fibrosis-related cardiac diseases.

Obesity, malnutrition, and the prevalence and outcome of hypertension: Evidence from the National Health and Nutrition Examination Survey.

Background: Nutritionally unhealthy obesity is a newly introduced phenotype characterized by a combined condition of malnutrition and obesity. This study aims to explore the combined influence of obesity and nutritional status on the prevalence and outcome of hypertension. Methods: Participants collected from the National Health and Nutrition Examination Survey (NHANES) database were divided into four subgroups according to their obesity and nutritional conditions, as defined by waist circumference and serum albumin concentration. The lean-well-nourished was set as the reference group. Logistic regression models were applied to evaluate the hypertension risk. Kaplan-Meier analysis and Cox proportional hazard regression models were used to assess the survival curve and outcome risk of participants with hypertension. Results: A total of 28,554 participants with 10,625 hypertension patients were included in the analysis. The lean-malnourished group showed a lower hypertension risk (odds ratio [OR] 0.85, 95% confidence interval [CI]: 0.77-0.94), while the obese-well-nourished condition elevated the risk (OR 1.47, 95% CI: 1.3-1.67). Two malnourished groups had higher mortality risks (HR 1.42, 95% CI: 1.12-1.80 and HR 1.31, 95% CI: 1.03-1.69 for the lean and obese, respectively) than the reference group. The outcome risk of the obese-well-nourished group (HR 1.02, 95% CI: 0.76-1.36) was similar to the lean-well-nourished. Conclusion: Malnutrition was associated with a lower risk of developing hypertension in both lean and obese participants, but it was associated with a worse outcome once the hypertension is present. The lean-malnourished hypertension patients had the highest all-cause mortality risk followed by the obese-malnourished. The obese-well-nourished hypertension patients showed a similar mortality risk to the lean-well-nourished hypertension patients.

Antifungal and antifeedant terpenoids from Paraphaeosphaeria sp. cultured by extract of host Ginkgo biloba.

Five undescribed terpenoids including a polyketide-terpenoid hybrid paraphaone, and four eremophilane sesquiterpenoids, paraphaterpenes A-D, as well as two known compounds were isolated from the endophytic fungus Paraphaeosphaeria sp. cultured by extract of host Ginkgo biloba L. The structures were established by spectroscopic analyses, and the single-crystal X-ray diffraction. The antifungal activity of Paraphaeosphaeria sp. cultured by extract of G. biloba against the plant pathogen Alternaria alternata was significant and higher than that of PDB medium. Tested compounds indicated antifeedant activities against silkworms with feeding deterrence index at 10-70%. Paraphaone, paraphaterpenes A, C, D and alternariol methyl ether showed significant antifungal activities against the phytopathogens A. alternata, Aspergillus fumigatus, and entomopathogen Beauveria bassiana with MICs ≤4 µg/mL. And the preliminary structure-activity relationship of eremophilane sesquiterpenoids was exhibited. The culture of Paraphaeosphaeria sp. by host G. biloba medium afforded agricultural antibiotics.

Three new fumagillol analogues and antifungal activity from Aspergillus fumigatus cocultured with Paraphaeosphaeria sp.

Two fungi Aspergillus fumigatus YXG-12-2, and Paraphaeosphaeria sp. YXG-18 were isolated from medicinal plant Ginkgo biloba. The interaction of endophytes and host could induce the productions of antifungal metabolites against pathogens for the plant resistance. Three new fumagillol analogues, fumiparaphines A-C were isolated from A. fumigatus cocultured with Paraphaeosphaeria sp. in host medium. New compounds 2, and 3 had the similar fumagillol structures with tetrahydrofuran or tetrahydropyrane residue. The structures were established by 1D, 2D NMR, mass spectrometry, and calculated ECD spectra. Fumiparaphine A (1) indicated significant antifungal activity against the phytopathogen Alternaria alternata with MIC of 2 µg/mL.

M1 macrophage-derived extracellular vesicle containing tsRNA-5006c promotes osteogenic differentiation of aortic valve interstitial cells through regulating mitophagy.

Background: Osteogenic differentiation of aortic valve interstitial cells (AVICs) plays a key role in the calcific aortic valve disease progression. Extracellular vesicles (EVs)-derived from M1-polarized macrophages (M1-EVs) orchestrated intercellular communication by delivering non-coding RNAs such as tRNA-derived small RNAs (tsRNAs) is crucial for cardiovascular disease. However, the role and mechanism of M1-EVs tsRNAs in osteogenic differentiation of AVICs remains largely unclear. Methods: M1-EVs and PBS treated-RAW 264.7 cell-derived EVs (NC-EVs) were incubated with AVICs and subjected to small RNA sequencing. Candidate tsRNA in M1-EVs was silenced to explore their effects on AVIC osteogenic differentiation and mitophagy. Results: DiI-labeled M1-EVs were internalized by AVICs, resulting in significantly increased calcium nodule formation and expression of osteogenesis-related genes in AVICs, including RUNX2, BMP2, osteopontin, and SPP1, compared with NC-EVs. Small RNA sequencing revealed that 17 tsRNAs were significantly up-regulated such as tsRNA-5006c, while 28 tsRNAs were significantly down-regulated in M1-EVs compared with NC-EVs. Intriguingly, tsRNA-5006c-deleted M1-EVs treatment significantly reduced calcium nodule formation and expression of osteogenesis-related genes in AVICs relative to control group. Moreover, target genes of tsRNA-5006c were mainly involved in autophagy-related signaling pathways, such as MAPK, Ras, Wnt, and Hippo signaling pathway. Hallmarks of mitophagy activation in AVICs including mitophagosome formation, TMRM fluorescence, expression of LC3-II, BINP3, and PGC1α, were significantly elevated in the M1-EVs group compared with NC-EVs group, whereas M1-EVs tsRNA-5006c inhibitor led to a significant reduction in these indicators. Conclusion: M1-EVs carried tsRNA-5006c regulates AVIC osteogenic differentiation from the perspective of mitophagy, and we provide a new target for the prevention and treatment of aortic valve calcification.

Structure of Waste Hemp Stalks and Their Sound Absorbing Properties.

To broaden the application fields of waste hemp stalks, the macromolecular, supramolecular, and morphological structures of waste hemp stalks were analyzed, and the relationship between these properties and the sound absorption properties of the hemp stalks was explored. Then, waste hemp stalk/polycaprolactone sound-absorbing composite materials were prepared by the hot pressing method. The influence of hemp stalk length and mass fraction, and the density and thickness of the composite materials on the sound absorption properties of composites prepared with the hot pressing temperature set to 140 °C, the pressure set to 8 MPa, and the pressing time set to 30 min was investigated. The results showed that, when the sound energy acts on the hemp stalk, the force between the chain segments, the unique hollow structure, and the large specific surface, act together to attenuate the sound energy and convert it into heat and mechanical energy in the process of propagation, to produce a good sound absorption effect. When the hemp stalk length and mass fraction were set to 6 mm and 50%, respectively, and the density and thickness of the material were set to 0.30 g/cm3 and 1.5 cm, respectively, the average sound absorption coefficient of the waste hemp stalk/polycaprolactone sound-absorbing composite material was 0.44, the noise reduction coefficient was 0.42, the maximum sound absorption coefficient was 1.00, and the sound-absorbing band was wide. The study provided an experimental and theoretical basis for the development of waste hemp stalk/polycaprolactone sound-absorbing composite materials, and provided a new idea for the recycling of the waste hemp stalk.

Dendrobine inhibits dopaminergic neuron apoptosis via MANF-mediated ER stress suppression in MPTP/MPP+-induced Parkinson's disease models.

BACKGROUND: Parkinson's disease (PD) is an age-related neurodegenerative disorder without effective treatments. Mesencephalic astrocyte-derived neurotrophic factor (MANF) has been suggested to be capable of protecting against PD by inhibiting endoplasmic reticulum (ER) stress-mediated neuronal apoptosis. PURPOSE: This study was aimed to evaluate the antiparkinsonian effect of dendrobine and reveal its underlying mechanisms from the perspective of MANF-mediated ER stress suppression. METHODS: Behavioral assessments of PD mice as well as LDH/CCK-8 assay in SH-SY5Y cells and primary midbrain neurons were carried out to detect the antiparkinsonian effect of dendrobine. Immunofluorescence, western blot, flow cytometry and shRNA-mediated MANF knockdown were used to determine the apoptosis of dopaminergic neurons and the expressions of ER stress-related proteins for investigating the underlying mechanism of dendrobine. RESULTS: Dendrobine significantly ameliorated the motor performance of PD mice and attenuated the injuries of dopaminergic neurons. Dendrobine could also relieve neuronal apoptosis, up-regulate MANF expression and inhibit ER stress, which were largely abolished by shRNA-mediated MANF knockdown in PD model. CONCLUSION: Dendrobine might protect against PD by inhibiting dopaminergic neuron apoptosis, which was achieved by facilitating MANF-mediated ER stress suppression. Our study suggested that dendrobine could act as a MANF up-regulator to protect against PD, and provided a potential candidate for exploring etiological agents of PD.

The production of broad-spectrum antibiotics from phytopathogen Epicoccum sorghinum by culturing in host edible mushroom Thelephora ganbajun extract.

Metabolism of special endophytes and phytopathogens can be induced by the symbiotic interactions with the host. A phytopathogen Epicoccum sorghinum cultured in host mushroom Thelephora ganbajun medium exhibited different metabolites compared with that of ordinary medium. An unprecedented scaffold possessing the same substructure as perylenequinone mycotoxin, a first methyl rearrangement product of phytotoxin, epoxydon 6-methylsalicylate ester, three undescribed compounds, and an undescribed natural product were isolated from E. sorghinum cultured in T. ganbajun. Episorin A and epicosorin A were produced from E. sorghinum induced by culturing in host medium. Episorin A was the first example of perylenequinone analogue in the natural products. These induced compounds and other metabolites showed notable antibiosis against endogenous fungi, and insect existing in mushroom. Induced episorin A showed significant inhibitory effects on nitric oxide production in LPS-activated macrophages, and anti-acetylcholinesterase with the IC50 at 5.40 ± 0.25 µM, and 4.32 µM, respectively, and cytotoxicity against HL-60, A-549, SMMC-7721, MCF-7 and SW480 with IC50 at 14.21 ± 0.53, 17.93 ± 0.22, 18.17 ± 0.63, 28.36 ± 0.43, and 18.20 ± 1.03 µM.

Effects of rice bran content on plant-based simulated meat: From the aspects of apparent properties and structural characteristics.

Rice Bran (RB) was added to soybean protein isolate (SPI) at 0%, 5%, 10%, 15% and 20% as addition to produce simulated meat by high moisture extrusion, and the apparent properties and structural characteristics of RB-SPI simulated meat were studied. The addition of 10% RB weakened the interaction among hydrogen bond (HB), hydrophobic bond (HI) and disulfide bond (DB), further increasing the hardness of simulated meat. Meanwhile, it decreased the content of intermolecular hydrogen bonding and enhanced the interaction between HI and HB, resulted in an increased tension. Adding 5% RB weakened the interaction between HB, HI and DB, decreased the content of random coils in the secondary structure, but strengthened the DB and ultimately increased the thermal stability of simulated meat.

Downregulation of miR-23b by transcription factor c-Myc alleviates ischemic brain injury by upregulating Nrf2.

Ischemic brain injury (IBI) is a common acute cerebral vessel disease that occurs secondary to blockage in arteries, mainly characterized by insufficient blood supply to the brain. The transcription factor c-Myc in IBI continues to be implicated in numerous studies. This study was conducted with emphasis placed on the underlying mechanism of c-Myc in IBI. Clinical samples were collected from IBI patients. Middle cerebral artery occlusion (MCAO) was induced in mice by inserting a suture from the external carotid artery to the anterior cerebral artery through the internal carotid artery to mechanically block the blood supply at the origin of the middle cerebral artery, and cortical neurons from mice were exposed to oxygen glucose deprivation (OGD) conditions for IBI model in vitro construction. RT-qPCR was performed to determine microRNA-23b (miR-23b) expression. TUNEL staining and Western blot analysis was conducted to detect apoptosis. The regulatory relationship was analyzed by dual-luciferase reporter gene assay. After loss- and gain-of-function assays, triphenyltetrazolium chloride staining was carried out to detect the area of cerebral infarction, after which the spatial memory in mice was evaluated with Morris water maze test. As per our findings, miR-23b was upregulated in the serum of IBI patients and OGD-treated murine primary neurons. Silencing of miR-23b resulted in reduced OGD-induced neuronal apoptosis. miR-23b inversely targeted nuclear factor erythroid 2-related factor 2 (Nrf2) and c-Myc negatively regulated miR-23b expression. Overexpression of c-Myc and inhibition of miR-23b led to reduced neurological scores of infarction area, neuronal apoptosis, shortened platform arrival time and significantly increased the time spent on the platform quadrant and the times of crossing the platform in vivo. Collectively, downregulated miR-23b by c-Myc might alleviate IBI by upregulating Nrf2.

The chemical diversity, the attractant, anti-acetylcholinesterase, and antifungal activities of metabolites from biocontrol Trichoderma harzianum uncovered by OSMAC strategy.

Eight new compounds (1-8) were discovered from Trichoderma harzianum associated with edible mushroom by the one strain many compounds (OSMAC) strategy. Triharzianin A (1) is the first naturally scaffold characterized by a C13-prostaglandin skeleton. The configurations of 1-3, and 5 were determined by the Mosher's method, experimental and calculated ECD spectra, and plausible biosynthesis of stereospecific epoxidation. Most compounds indicated obvious feeding attractant activities to silkworm with attraction rates at 30-90%. Compound 7 showed anti-acetylcholinesterase (anti-AChE) activity with a ratio of 29% at a concentration of 50 µM for insecticidal potential. So 2,​3-​dialkylchromone (7) had potential of chemical entrapment and killing of insects. Compounds 2, 3 and 7-11 showed antifungal activities against Aspergillus fumigates, and Trichoderma sp. from mushroom with MICs ≤ 300 µM. The four fermentation extracts also indicated obvious feeding attractant activities to silkworm for the activities brought by active metabolites from T. harzianum. The material base of biocontrol induced by the interaction of host-fungal symbiont can be investigated by the antifungal metabolites against pathogen fungi.

Paroxysmal Sympathetic Hyperactivity in Severe Anti-N-Methyl-d-Aspartate Receptor Encephalitis: A Single Center Retrospective Observational Study.

Background: Paroxysmal sympathetic hyperactivity (PSH) is a disorder with excessive sympathetic activity commonly recognized in patients with acquired brain injury. Autonomic instability is frequent in anti-N-methyl-d-aspartate receptor encephalitis (anti-NMDARE). However, PSH in anti-NMDARE has gained little attention. Methods: We retrospectively reviewed 24 patients diagnosed with severe anti-NMDARE in the neuro-intensive care unit (NICU) between 2014 and 2019. Patients were assessed with the PSH assessment measure (PSH-AM) scale, and categorized into "PSH+" group and "PSH-" group. The clinical characteristics, hospital mortality, and functional outcome by modified Rankin Scale (mRS) score at six months after discharge were compared between the two groups. Among patients with PSH+, the clinical features and pharmacotherapy of PSH were summarized and compared. Results: Twenty-four patients were included in the study. Twelve of them (50%) were categorized as PSH+ based on PSH-AM scores. There were no significant differences in the demographic characteristic, GCS scores upon admission, incidence of status epilepticus, teratoma occurrence, hospital mortality, and 6-month mRS between PSH+ and PSH- groups. Patients with PSH+ had increased length of NICU stay, hospital stay and duration of mechanical ventilation. The most prominent clinical features of PSH in severe anti-NMDARE were tachycardia and hyperthermia, while posturing was the relatively mildest clinical feature. Propranolol and clonazepam were more commonly used than gabapentin in pharmacotherapy of PSH in severe anti-NMDARE. Conclusions: The incidence of PSH in severe anti-NMDARE patients was as high as 50%. Patients with PSH demonstrated prolonged NICU stay, hospital stay and increased duration of mechanical ventilation, while no effect on hospital mortality and functional outcome. Clinicians should be aware of the distinctive characteristics and treatment options of PSH in severe anti-NMDARE.

LncRNA-H19 Drives Cardiomyocyte Senescence by Targeting miR-19a/socs1/p53 Axis.

Purpose: Cardiomyocyte senescence is associated with a progressive decline in cardiac physiological function and the risk of cardiovascular events. lncRNA H19 (H19), a well-known long noncoding RNA (lncRNA), is involved in the pathophysiological process of multiple cardiovascular disease such as heart failure, cardiac ischemia and fibrosis. However, the role of H19 in cardiomyocyte senescence remains to be further explored. Methods: Senescence-associated ß-galactosidases (SA-ß-gal) staining was used to detect cardiomyocyte senescence. Western blot, qRT-PCR and luciferase reporter assay were employed to evaluate the role of H19 in cardiomyocyte senescence and its underling molecular mechanism. Results: H19 level was significantly increased in high glucose-induced senescence cardiomyocytes and aged mouse hearts. Overexpression of H19 enhanced the number of SA-ß-gal-positive cells, and the expression of senescence-related proteins p53 and p21, whereas H19 knockdown exerted the opposite effects. Mechanistically, H19 was demonstrated as a competing endogenous RNA (ceRNA) for microRNA-19a (miR-19a): H19 overexpression downregulated miR-19a level, while H19 knockdown upregulated miR-19a. The expression of SOSC1 was dramatically increased in senescence cardiomyocytes and aged mouse hearts. Further experiments identified SOCS1 as a downstream target of miR-19a. H19 upregulated SOCS1 expression and activated the p53/p21 pathway by targeting miR-19a, thus promoting the cardiomyocytes senescence. Conclusion: Our results show that H19 is a pro-senescence lncRNA in cardiomyocytes acting as a ceRNA to target the miR-19a/SOCS1/p53/p21 pathway. Our research reveals a molecular mechanism of cardiomyocyte senescence regulation and provides a novel target of the therapy for senescence-associated cardiac diseases.

SAIL: a new conserved anti-fibrotic lncRNA in the heart.

Long non-coding RNAs (lncRNAs) account for a large proportion of genomic transcripts and are critical regulators in various cardiac diseases. Though lncRNAs have been reported to participate in the process of diverse cardiac diseases, the contribution of lncRNAs in cardiac fibrosis remains to be fully elucidated. Here, we identified a novel anti-fibrotic lncRNA, SAIL (scaffold attachment factor B interacting lncRNA). SAIL was reduced in cardiac fibrotic tissue and activated cardiac fibroblasts. Gain- and loss-of-function studies showed that knockdown of SAIL promoted proliferation and collagen production of cardiac fibroblasts with or without TGF-ß1 (transforming growth factor beta1) treatment, while overexpression of SAIL did the opposite. In mouse cardiac fibrosis induced by myocardial infarction, knockdown of SAIL exacerbated, whereas overexpression of SAIL alleviated cardiac fibrosis. Mechanically, SAIL inhibited the fibrotic process by directly binding with SAFB via 23 conserved nucleotide sequences, which in turn blocked the access of SAFB to RNA pol II (RNA polymerase II) and reduced the transcription of fibrosis-related genes. Intriguingly, the human conserved fragment of SAIL (hSAIL) significantly suppressed the proliferation and collagen production of human cardiac fibroblasts. Our findings demonstrate that SAIL regulates cardiac fibrosis by regulating SAFB-mediated transcription of fibrotic related genes. Both SAIL and SAFB hold the potential to become novel therapeutic targets for cardiac fibrosis.

In vitro antimicrobial activity and comparison of the herbal extracts and sodium hypochlorite against primary plaque colonizers.

NaClO is not suitable as a root canal irrigant because of its cytotoxicity. Good biocompatibility irrigants are required to have antibacterial activity. Many herbal products like Bee glue, Noni juice and Azadirachta indica have such properties. This study aims to investigate the possible effects of propolis, MCJ and Neem on bacterial infections and cytotoxicity in primary plaque colonizers. Direct contact and agar diffusion tests evaluated the antibacterial activity of herbal products against Fusobacterium, Candida albicans and Prevotella. The CCK 8 test determined the influence of these herbal products on the proliferation of human apical papilla stem cells (hSCAPs) and human periodontal fibroblasts (hPDLFs). A migration assay test was performed in addition to quantitative real-time PCR which measured osteogenic differentiation in hSCAPs. All herbal extracts tested in this study exhibited antibacterial activity comparable to NaClO against bacterial infections, while the strongest bacteriostatic effect was shown in the herbal treated group. These extracts had much weaker effects on the proliferation and migration of hSCAPs and hPDLFs as calculated by the CCK-8 assay against NaClO. Bee glue treatment had the most potent effect on osteogenic differentiation, followed by treatment with Noni juice and Azadirachta indica (Neem), while NaClO showed the lowest effect. For primary plaque colonizers of immature or advanced permanent teeth, Bee glue, Noni juice, and Azadirachta indica can be promising irrigants with good biocompatibility. Direct contact process and agar diffusion studies have tested the antibacterial activity against Fusobacterium, Candida albicans and Prevotella. The CCK 8 test determined the influence of these three plants on the proliferation of human apical papilla stem cells (hSCAPs) and human periodontal fibroblasts (hPDLFs). In order to examine migration ability, migration assay test was performed. Alizarin red staining, alkaline phosphatase (ALP) staining and quantitative real-time PCR measured osteo-/odontogenic differentiation in hSCAPs. All herbal extracts tested in this study exhibited antibacterial activity comparable to NaClO against bacterial infections, while the strongest bacteriostatic effect was shown in the treated group. These extracts had much weaker effects on the proliferation and migration of hSCAPs and hPDLFs as calculated by the CCK-8 assay against NaClO. Bee glue treatment had the most potent effect on osteo-odontogenic differentiation, followed by treatment with Noni juice and Azadirachta indica (Neem), while NaClO showed the lowest effect. For primary plaque colonizers of immature or advanced permanent teeth, Bee glue, Noni juice and Azadirachta indica (Neem) can be promising irrigants.

Silencing of METTL3 attenuates cardiac fibrosis induced by myocardial infarction via inhibiting the activation of cardiac fibroblasts.

Cardiac fibrosis is characterized by the activation of cardiac fibroblasts and accumulation of extracellular matrix. METTL3, a component of methyltransferase complex, participates in multiple biological processes associated with mammalian development and disease progression. However, the role of METTL3 in cardiac fibrosis is still unknown. We performed fibroblasts activation with TGF-ß1 (20 ng/mL) in vitro and established in vivo mouse models with lentivirus to assess the effects of METTL3 on cardiac fibroblasts proliferation and collagen formation. Methylated RNA immunoprecipitation (MeRIP) was used to define the potential fibrosis-regulated gene. The expression level of METTL3 was increased in cardiac fibrotic tissue of mice with chronic myocardial infarction and cultured cardiac fibroblats (CFs) treated with TGF-ß1. Enforced expression of METTL3 promoted proliferation and fibroblast-to-myofibroblast transition and collagens accumulation, while silence of METTL3 did the opposite. Silence of METTL3 by lentivirus carrying METTL3 siRNA markedly alleviated cardiac fibrosis in MI mice. Transcriptome and N6-methyladenosine (m6 A) profiling analyses revealed that the expression and m6 A level of collagen-related genes were altered after silence of METTL3. METTL3-mediated m6 A modification is critical for the development of cardiac fibrosis, providing a molecular target for manipulating fibrosis and the associated cardiac diseases.