Melatonin attenuated chronic visceral pain by reducing Nav1.8 expression and nociceptive neuronal sensitization.

BACKGROUND: Irritable bowel syndrome (IBS) is a common functional gastrointestinal disorder, and its specific pathogenesis is still unclear. We have previously reported that TTX-resistant (TTX-R) sodium channels in colon-specific dorsal root ganglion (DRG) neurons were sensitized in a rat model of visceral hypersensitivity induced by neonatal colonic inflammation (NCI). However, the detailed molecular mechanism for activation of sodium channels remains unknown. This study was designed to examine roles for melatonin (MT) in sensitization of sodium channels in NCI rats. METHODS: Colorectal distention (CRD) in adult male rats as a measure of visceral hypersensitivity. Colon-specific dorsal root ganglion (DRG) neurons were labeled with DiI and acutely dissociated for measuring excitability and sodium channel current under whole-cell patch clamp configurations. Western blot and Immunofluorescence were employed to detect changes in expression of Nav1.8 and MT2. RESULTS: The results showed that rats exhibited visceral hypersensitivity after NCI treatment. Intrathecal application of melatonin significantly increased the threshold of CRD in NCI rats with a dose-dependent manner, but has no role in the control group. Whole-cell patch clamp recording showed that melatonin remarkably decreased the excitability and the density of TTX-R sodium channel in DRG neurons from NCI rats. The expression of MT2 receptor at the protein level was markedly lower in NCI rats. 8MP, an agonist of MT2 receptor, enhanced the distention threshold in NCI rats. Application of 8MP reversed the enhanced hypersensitivity of DRG neurons from NCI rats. 8MP also reduced TTX-R sodium current density and modulated dynamics of TTX-R sodium current activation. CONCLUSIONS: These data suggest that sensitization of sodium channels of colon DRG neurons in NCI rats is most likely mediated by MT2 receptor, thus identifying a potential target for treatment for chronic visceral pain in patients with IBS.

Analysis of hemi-uterus pregnancy outcomes in uterine malformations: a retrospective observational study.

BACKGROUND: The association between uterine malformations and adverse pregnancy outcomes is well recognized. However, studies on adverse pregnancy outcomes based on one kind of anatomical commonality between different uterine anomalies have not been reported. This study aimed to investigate pregnancy outcomes in pregnancies with uterine malformations when the pregnancy is confined to a hemi-uterus. METHODS: A retrospective observational study of 336 women who gave birth at our hospital from 2015 to 2021 was performed. Women (n = 112) with a unicornuate, complete bicornuate, or didelphic uterus were set as the study group, and women (n = 224) with a normal uterus were set as the reference group. Maternal and neonatal outcomes were evaluated and compared between the two groups using Student's t-test, one-way ANOVA, Chi-squared test, Yates correction for continuity, or Fisher's exact test. Modified Poisson regression analyses were used to estimate the relationships between the hemi-uterus pregnancy and preterm birth, preterm premature rupture of membranes, and cesarean section rates by adjusting for potential confounders. A P value < 0.05 was considered significant. RESULTS: Women in the study group had a higher history of spontaneous abortion (24.1% vs. 10.7%, P = 0.002) and intrauterine fetal death (5.4% vs. 0.4, P = 0.006). Compared with the reference group, the study group had significantly higher rates of assisted reproductive technology (9.4% vs. 2.2%, P = 0.001) and cord-around-the neck (54.5% vs. 29.9%, P = 0.000). Modified Poisson regression analyses showed that the study group was at higher risk for preterm birth (aRR, 6.8; 95% CI 2.7-16.7), preterm premature rupture of membranes (aRR, 14.1; 95% CI 3.2-62.5), malpresentation (aRR, 13.2; 95% CI 6.3-27.7), and cesarean section (aRR, 4.4; 95% CI 3.3-5.7). CONCLUSION: Women with a unicornuate, didelphic, or complete bicornuate uterus are at higher risk for some adverse pregnancy outcomes than those with a normal uterus.

An endophytic fungus Schizophyllum commune isolated from Panax ginseng enhances hairy roots growth and ginsenoside biosynthesis.

Using endophytic fungal elicitors to increase the accumulation of valuable secondary metabolites in plant tissue culture is an effective biotechnology strategy. In this study, a collection of 56 strains of endophytic fungi were isolated from different organs of cultivated Panax ginseng, of which seven strains can be symbiotically co-cultured with the hairy roots of P. ginseng. Further experiments observed that strain 3R-2, identified as endophytic fungus Schizophyllum commune, can not only infect hairy roots but also promote the accumulation of specific ginsenosides. This was further verified because S. commune colonization significantly affected the overall metabolic profile of ginseng hairy roots. By comparing the effects of S. commune mycelia and its mycelia extract (EM) on ginsenoside production in P. ginseng hairy roots, the EM was confirmed to be a relatively better stimulus elicitor. Additionally, the introduction of EM elicitor can significantly enhance the expressions of key enzyme genes of pgHMGR, pgSS, pgSE, and pgSD involved in the biosynthetic pathway of ginsenosides, which was deemed the most relevant factor for promoting ginsenosides production during the elicitation period. In conclusion, this study is the first to show that the EM of endophytic fungus S. commune can be considered as an effective endophytic fungal elicitor for increasing the biosynthesis of ginsenosides in hairy root cultures of P. ginseng.

Comparison of the total and hidden blood loss in patients undergoing single-level open and unilateral biportal endoscopic transforaminal lumbar interbody fusion: a retrospective case control study.

PURPOSE: This study aimed to compare total blood loss (TBL) and hidden blood loss (HBL) in patients undergoing single-level open transforaminal lumbar interbody fusion (O-TLIF) and unilateral biportal endoscopic transforaminal lumbar interbody fusion (ULIF). METHODS: A total of 53 patients who underwent ULIF and 53 patients who underwent O-TLIF from March 2020 to July 2022 were retrospectively reviewed. The Nadler's formula was employed to estimate the patient's blood volume (PBV), Gross's formula to estimate TBL, and Sehat's formula to estimate HBL. The obtained data were then analyzed with independent t test, chi-squared test, and analysis of covariance. RESULTS: TBL and measured blood loss (MBL) in ULIF group (326.86 ± 223.45 ml, 99.00 ± 72.81 ml) was significantly lower than O-TLIF group (427.97 ± 280.52 ml, 270.66 ± 102.34 ml). Nevertheless, the HBL in ULIF group was higher than that in O-TLIF group (227.86 ± 221.75 ml vs 157.31 ± 268.08 ml), however this was not statistically significant (p = 0.143). The HBL was 69.71 ± 23.72% of TBL in ULIF group and 36.76 ± 18.79% of TBL in O-TLIF group. Patients in ULIF group had lower TBL and MBL, shorter duration of drainage, lower postoperative anemia, and shorter postoperative hospital stay compared to those in O-TLIF group. CONCLUSIONS: Perioperative HBL should not be neglected in patients undergoing ULIF or O-TILF, as it accounts for a large percentage of TBL in both groups. ULIF is associated with lower TBL and MBL, postoperative anemia, shorter postoperative hospital stays compared with O-TLIF.

Simulations of the Characteristics of the Entropy Mode in Dipole-Magnetic-Confined Plasmas.

Plasmas confined in a dipole magnetic field widely exist in both space and laboratories, and this kind of plasma draws much attention from researchers both in plasma physics and in space science. In this paper, the characteristics of the collisionless electrostatic instability of the entropy mode in a dipole-magnetic-confined plasma are simulated with the linear gyrokinetic model. It is found that the entropy mode can be generated in dipole-magnetic-confined plasmas, and there are two typical stages of the entropy mode, with another transitional stage at different values of η. The main instability changes from the ion diamagnetic drift to the electronic diamagnetic drift as η becomes larger. In addition, the MHD mode predicts that the most stable point is at η~2/3 when k⟂ρi << 1. However, we find that η and k⟂ρi are coupled with each other, and the most stable point of the mode moves gradually to η~1 as k⟂ρi increases. There is a peak value for the entropy mode growth rate around k⟂ρi~1.0, and more complicated modes are induced so that the dispersion relation has been changed when the driving force of the plasma pressure gradient effect is obvious. For example, the characteristics of the interchange-like modes gradually emerge when the driving effect of the plasma pressure becomes stronger. Further investigations should be taken to reveal the characteristics of the entropy mode in magnetospheric plasmas.

Transcriptome sequencing and signal transduction for the enhanced tanshinone production in Salvia miltiorrhiza hairy roots induced by Trichoderma atroviride D16 polysaccharide fraction.

Salvia miltiorrhiza Bunge. is commonly used to treat vascular diseases because of its activity ingredients, phenolic acids, and tanshinones. Polysaccharide fraction (PSF) extracted from Trichoderma atroviride D16 could promote tanshinone accumulation in S. miltiorrhiza hairy roots. Transcriptome sequencing was conducted to describe the global gene expression of PSF-treatment hairy roots, and data analyses showed enzymes of tanshinone biosynthetic pathways were up-regulated, and genes associated to signal molecules and transcription factors were responsive. Endogenous H2O2, abscisic acid, and nitric oxide contents were measured after PSF treatment, while tanshinone accumulations were measured with treatment of exogenous H2O2 or H2O2 inhibitor on PSF-treatment S. miltiorrhiza hairy roots. The results showed H2O2 was important in tanshinone biosynthesis caused by PSF and nitric oxide might be the downstream molecules of H2O2. Taken together, the study indicates that D16 PSF enhances the accumulation of tanshinones through enzymes of tanshinone biosynthetic pathways, signal molecules, and transcription factors.

Retinoic Acid Receptor Gamma (RARγ) Promotes Cartilage Destruction through Positive Feedback Activation of NF-κB Pathway in Human Osteoarthritis.

Osteoarthritis (OA) is a severe inflammation-related disease which leads to cartilage destruction. The retinoic acid receptor gamma (RARγ) has been indicated to be involved in many inflammation processes. However, the role and mechanism of RARγ in cartilage destruction caused by inflammation in OA are still unknown. Here, we demonstrated that the RARγ was highly expressed in chondrocytes of OA patients compared with healthy people and was positively correlated with the damage degree of cartilage in OA. Cytokine TNF-α promoted the transcription and expression of RARγ through activating the NF-κB pathway in OA cartilage. In addition, the overexpression of RARγ resulted in the upregulation of matrix degradation and inflammation associated genes and downregulation of differentiation and collagen production genes in human normal chondrocyte C28/I2 cells. Mechanistically, overexpression of RARγ could increase the level of p-IκBα and p-P65 to regulate the expression of downstream genes. RARγ and IκBα also could interact with each other and had the same localization in C28/I2 cells. Moreover, the SD rats OA model induced by monosodium iodoacetate indicated that CD437 (RARγ agonist) and TNF-α accelerated the OA progression, including more severe cartilage layer destruction, larger knee joint diameter, and higher serum ALP levels, while LY2955303 (RARγ inhibitor) showed the opposite result. RARγ was also highly expressed in OA group and even higher in TNF-α group. In conclusion, RARγ/NF-κB positive feedback loop was activated by TNF-α in chondrocyte to promote cartilage destruction. Our data not only propose a novel and precise molecular mechanism for OA disease but also provide a prospective strategy for the treatment.

The novel use of lauromacrogol: A respective study of ultrasound-guided sclerosant injection for cesarean scar pregnancy.

AIM: To introduce the novel use of lauromacrogol for cesarean scar pregnancy (CSP), and to compare the clinical efficacy and safety of curettage combined with ultrasound-guided sclerosant injection (USI) and curettage following uterine artery embolization (UAE) in the treatment of CSP. METHODS: CSP patients undergoing curettage combined with USI (n = 72) from December 2014 to May 2020 were compared to patient with curettage following UAE (n = 72).The basic clinical findings and clinical outcomes were reviewed between the two groups. RESULTS: For USI group, 69 patients underwent successful treatment (95.8% success rate), while the number of cured patients for the UAE group was 70 (97.2% success rate). Differences between USI group and UAE group in intraoperative blood loss (10.0 [10.0-20.0] vs. 10.0 [10.0-20.0] mL) and time for serum ß human chorionic gonadotropin (ß-hCG) to reduce to normal (28.0 [21.0-40.0] vs. 28.0 [21.0-35.0] days) were not statistically significant. The hospital stay for USI group was significantly shorter than that for UAE group (4.0 [4.0-6.0] vs. 6.0 [5.0-7.0] days, respectively). Statistically significant decreases were noted in hospitalization expenses and adverse events in USI group, compared to UAE group. There was no difference in live birth rate between the two groups with fertility intentions during the follow-up. CONCLUSION: For treatment of CSP, curettage combined with USI yielded clinical results comparable to those of curettage following UAE. Curettage combined with USI was associated with lower hospitalization expenses, shorter hospital stay and less complications, and it merited an effective and safe treatment for CSP.

Transcriptional regulation of telomeric repeat-containing RNA by acridine derivatives.

Telomere is a specialized DNA-protein complex that plays an important role in maintaining chromosomal integrity. Shelterin is a protein complex formed by six different proteins, with telomeric repeat factors 1 (TRF1) and 2 (TRF2) binding to double-strand telomeric DNA. Telomeric DNA consists of complementary G-rich and C-rich repeats, which could form G-quadruplex and intercalated motif (i-motif), respectively, during cell cycle. Its G-rich transcription product, telomeric repeat-containing RNA (TERRA), is essential for telomere stability and heterochromatin formation. After extensive screening, we found that acridine derivative 2c and acridine dimer DI26 could selectively interact with TRF1 and telomeric i-motif, respectively. Compound 2c blocked the binding of TRF1 with telomeric duplex DNA, resulting in up-regulation of TERRA. Accumulated TERRA could bind with TRF1 at its allosteric site and further destabilize its binding with telomeric DNA. In contrast, DI26 could destabilize telomeric i-motif, resulting in down-regulation of TERRA. Both compounds exhibited anti-tumour activity for A549 cells, but induced different DNA damage pathways. Compound 2c significantly suppressed tumour growth in A549 xenograft mouse model. The function of telomeric i-motif structure was first studied with a selective binding ligand, which could play an important role in regulating TERRA transcription. Our results showed that appropriate level of TERRA transcript could be important for stability of telomere, and acridine derivatives could be further developed as anti-cancer agents targeting telomere. This research increased understanding for biological roles of telomeric i-motif, TRF1 and TERRA, as potential anti-cancer drug targets.

Isolated fallopian tube torsion with paraovarian cysts: a case report and literature review.

BACKGROUND: Isolated fallopian tube torsion (IFTT) is a rare cause of gynecological acute abdomen, is easily misdiagnosed and often has a delay in diagnosis. IFTT with paraovarian cysts is most frequently reported in studies. Here, we reported a patient diagnosed with IFTT associated with a paraovarian cyst, and we conducted a literature review for IFTT, aiming to identify valuable information that will be helpful for diagnosis and treatment for fallopian tube torsions. CASE PRESENTATION: A 13-year-old girl presented with a 10-day history of right lower abdominal pain that worsened 2 days before presentation. On presentation, ultrasound showed a 5.8 * 5.5 cm hypoechoic cyst adjacent to the right ovary, and between the cyst and ovary, a tortuous thickened tube was visualized. Laparoscopy revealed a triple torsion of the right fallopian tube with a 6-cm paraovarian cyst, and tubal conservation surgery was performed. The postoperative course was uneventful. Histopathological diagnosis revealed serous papillary cystadenoma. CONCLUSION: Paraovarian cystic dilatation often occurs in adolescence and can induce fallopian torsion when the size of the cyst reaches 5-cm. In our review, the median age of patients diagnosed with IFTT with paraovarian cysts was 15 years old, and the main clinical manifestation was emergency abdominal pain. The associated symptoms were variable, and vomiting was the most commonly associated symptom. Salpingectomy was the most common procedure performed; however, timely surgical intervention can effectively avoid salpingectomy.

PG-SGA SF in nutrition assessment and survival prediction for elderly patients with cancer.

BACKGROUND: This study was sought to report the prevalence of malnutrition in elderly patients with cancer. Validate the predictive value of the nutritional assessment tool (Patient-Generated Subjective Global Assessment Short Form, PG-SGA SF) for clinical outcomes and assist the therapeutic decision. METHODS: This is a secondary analysis of a multicentric, observational cohort study. Elderly patients with cancer older than 65 years were enrolled after the first admission. Nutritional status was identified using the PG-SGA SF. RESULTS: Of the 2724 elderly patients included in the analysis, 65.27% of patients were male (n = 1778); the mean age was 71.00 ± 5.36 years. 31.5% of patients were considered malnourished according to PG-SGA SF. In multivariate analysis, malnutrition(PG-SGA SF > 5) was significantly associated with worse OS (HR: 1.47,95%CI:1.29-1.68), affects the quality of life, and was related to more frequent nutrition impact symptoms. During a median follow-up of 4.5 years, 1176 death occurred. The mortality risk was 41.10% for malnutrition during the first 12 months and led to a rate of 323.98 events per-1000-patient-years. All nutritional assessment tools were correlated with each other (PG-SGA SF vs. PG-SGA: r = 0.98; PG-SGA SF vs. GLIM[Global Leadership Initiative on Malnutrition]: r = 0.48, all P < 0.05). PG-SGA SF and PG-SGA performed similarly to predict mortality but better than GLIM. PG-SGA SF improves the predictive ability of the TNM classification system for mortality in elderly patients with cancer, including distinguishing patients' prognoses and directing immunotherapy. CONCLUSIONS: The nutritional status as measured by PG-SGA SF which is a prognostic factor for OS in elderly cancer patients and could improve the prognostic model of TNM.

Modeling and Evaluation of Piezoelectric Transducer (PZT)-Based Through-Metal Energy and Data Transfer.

Through-metal transfer of energy and data using piezoelectric transduce can avoid the potential leakage problem caused by physical penetrations and wired feed-through. The through-metal transfer efficiency of energy or data is determined by the relative pressure on the receiving PZT (piezoelectric transducer). Hence, in this paper, we first propose the Spatial Equivalent Plane Acoustic Pressure (SEPAP), which is defined as the integration of the acoustic pressure over the receiving area, to model the pressure on the receiving PZT. Then we analyze the features of SEPAP and the factors impacting it by utilizing COMSOL. Furthermore, we propose a low-cost and small-size prototype for simultaneous transfer of energy and bidirectional communication through metal by using two pairs of PZTs working on different resonant frequencies. Extensive experiment has been done on evaluating the match between SEPAP transfer efficiency and the power transfer efficiency and analyzing the achievable data rate for bi-directional communication. Test through a 20 mm aluminum alloy plate shows that power transmission with efficiency 20.3% and data communication rate up to 38.4 Kbps can be achieved simultaneously.

[Quality evaluation of angelica broken wall powder based on QbD concept of traditional Chinese medicine].

In this paper, angelica broken wall powder(ABWP) was taken as the research object, HPLC fingerprint combined with multi-component determination(ferulic acid, senkyunolide I, coniferyl ferulate, ligustilide and 3-butylidenephthalide), physical fingerprint(D_(90), particle size distribution range, particle size distribution width, bulk density, tap density, inter-particle porosity, Carr index, specific surface area, pore volume, angle of repose, Hausner ratio, loss on drying and hygroscopicity)were used to characterize the quality attribute of ABWP; similarity analysis, cluster analysis, principal component analysis and orthogonal partial least squares discriminant analysis were conducted to construct the quality evaluation method of holographic analysis based on traditional Chinese medicine QbD "4 H mode", in order to evaluate the quality of ABWP from different sources and find out differentiated indicators. The quality evaluation method could be used for scientific, comprehensive evaluation of the quality attribute of ABWP, and the quality consistency evaluation of cell-wall-broken powder of different sources or different processes.It provides new ideas for quality control and research of ultrafine granular powders of traditional Chinese medicine.

Palladium-Catalyzed Desulfitative Cross-Coupling of Arylsulfonyl Hydrazides with Terminal Alkynes: A General Approach toward Functionalized Internal Alkynes.

A palladium-catalyzed Sonogashira-type coupling between arylsulfonyl hydrazides and terminal alkynes via Ar(C)-S bond cleavage is disclosed, which enables the general synthesis of functionalized internal alkynes, especially the Br-substituted ones, in good to excellent yields under acid- and base-free conditions.

Endophytic fungi with antitumor activities: Their occurrence and anticancer compounds.

Plant endophytic fungi have been recognized as an important and novel resource of natural bioactive products, especially in anticancer application. This review mainly deals with the research progress on the production of anticancer compounds by endophytic fungi between 1990 and 2013. Anticancer activity is generally associated with the cytotoxicity of the compounds present in the endophytic fungi. All strains of endophytes producing antitumor chemicals were classified taxonomically and the genera of Pestalotiopsis and Aspergillus as well as the taxol producing endophytes were focused on. Classification of endophytic fungi producing antitumor compounds has received more attention from mycologists, and it can also lead to the discovery of novel compounds with antitumor activity due to phylogenetic relationships. In this review, the structures of the anticancer compounds isolated from the newly reported endophytes between 2010 and 2013 are discussed including strategies for the efficient production of the desired compounds. The purpose of this review is to provide new directions in endophytic fungi research including integrated information relating to its anticancer compounds.

Medicinal plant cell suspension cultures: pharmaceutical applications and high-yielding strategies for the desired secondary metabolites.

The development of plant tissue (including organ and cell) cultures for the production of secondary metabolites has been underway for more than three decades. Plant cell cultures with the production of high-value secondary metabolites are promising potential alternative sources for the production of pharmaceutical agents of industrial importance. Medicinal plant cell suspension cultures (MPCSC), which are characterized with the feature of fermentation with plant cell totipotency, could be a promising alternative "chemical factory". However, low productivity becomes an inevitable obstacle limiting further commercialization of MPCSC and the application to large-scale production is still limited to a few processes. This review generalizes and analyzes the recent progress of this bioproduction platform for the provision of medicinal chemicals and outlines a range of trials taken or underway to increase product yields from MPCSC. The scale-up of MPCSC, which could lead to an unlimited supply of pharmaceuticals, including strategies to overcome and solution of the associated challenges, is discussed.

Analysis of the Morphology of Maxillary Sinus Septa on Reconstructed Cone-Beam Computed Tomography Images.

PURPOSE: Preoperative assessment of maxillary sinus anatomy can prevent complications associated with sinus grafting or implant procedures. The purpose of this study was to measure the frequency, numbers, locations, orientations, and heights of maxillary sinus septa. MATERIALS AND METHODS: Reconstructed cone-beam computed tomographic images of 1,012 sinuses were analyzed using NewTom VG software (NNT 2.21, ImageWorks, Elmsford, NY). This cross-sectional study included patients who underwent radiography at the department of radiology. The presence, numbers, locations, orientations, and heights of septa were analyzed. To establish multiple predictors in this study, groups were defined according to different radiographic features of the septa. Differences between male and female groups and between edentulous and dentulous groups were tested with χ(2) tests and the level of significance was set at 5%. RESULTS: The sample consisted of 506 patients (168 men and 338 women; average age, 35.1 yr). A significantly (P < .05) greater occurrence rate of 57.4% was observed in the edentulous group compared with the rate of 39.7% observed in the dentulous group. CONCLUSIONS: The difference in the prevalence of maxillary sinus septa between the edentulous and dentulous groups was statistically significant (P < .05), and the septa exhibited variable characteristics. It is essential and effective to analyze computed tomographic images of sinuses to evaluate the characteristics of septa before performing surgical procedures.

Gibberella moniliformis AH13 with antitumor activity, an endophytic fungus strain producing triolein isolated from Adlay (Coix lacryma-jobi: poaceae).

In this study, the isolation of an endophytic fungus from the leaves of the medicinal herb adlay (Coix lacryma-jobi L. var. ma-yuen Stapf) is reported for the first time. The fungus produced Triolein (trioleoylglycerol), a major constituent of triacylglycerols (TAGs) of adlay, in rice medium under shake-flask and bench-scale fermentation conditions. The fungus was identified as Gibberella moniliformis (Fusarium verticillioides) by its morphology and authenticated by ITS analysis (ITS1 and ITS2 regions and the intervening 5.8S rDNA region). Triolein was identified by HPLC-ELSD coupled with APCI-MS and confirmed through comparison with authentic standard. The concentration of triolein produced by G. moniliformis AH13 reached 2.536 ± 0.006 mg/g dry weight of mycelium. Moreover, the EtOAc extract of G. moniliformis AH13 showed strong antitumor activity against four types of tumor cells (A549, HCT116, MDA-MB-231, and SW1990). These results suggest that G. moniliformis AH13 in adlay has significant scientific and industrial potential to meet the pharmaceutical demands and sustainable energy requirements for TAGs in a cost-effective, easily accessible, and reproducible way and is also a potential novel source of natural antitumor bioactive agents.

Diosmetin ameliorates osteoarthritic inflammation in vivo and ECM macromolecules degradation in interleukin-1ß-stimulated murine chondrocytes through the Nrf2/NF-κB pathway.

INTRODUCTION: Osteoarthritis (OA) is a prevailing degenerative disease in elderly population and can lead to severe joint dysfunction. Studies have revealed various pharmacological activities of diosmetin, including the anti-OA efficacy. The present study further investigated its effect on interleukin (IL)-1ß-induced OA in chondrocytes. MATERIAL AND METHODS: Primary chondrocytes were isolated from young mice, stimulated with IL-1ß (10 ng/mL), and pretreated with diosmetin (10 and 20 µM) to conduct the in vitro assays. CCK-8 assay assessed the cytotoxicity of diosmetin whereas the levels of inflammatory factors (PGE2, nitrite, TNF-α, and IL-6) in homogenized cells were evaluated by ELISA. The levels of inflammatory cytokines, content of extracellular matrix (ECM), and signaling-related proteins (Nrf2, HO-1, and NF-κB p65) were assessed by western blotting. Expression of collagen II, p65, and Nrf2 in the chondrocytes was confirmed by immunofluorescence staining. The chondrocytes treated with IL-1ß and diosmetin were transfected with Nrf2 knockdown plasmid (si-Nrf2) to investigate the role of Nrf2. In vivo OA mouse model was induced by surgically destabilizing the medial meniscus (DMM). Safranin O staining was conducted to assess the OA severity in the knee-joint tissue. RESULTS: Diosmetin suppressed the expression of iNOS, COX-2, PGE2, nitrite, TNF-α, IL-6, MMP-13, and ADAMTS-5 induced by IL-1ß in chondrocytes. The expression of p-p65, p-IκBα, and nuclear p65 was decreased whereas that of Nrf2 and HO-1 increased by diosmetin treatment in IL-1ß-treated chondrocytes. Nrf2 knockdown by siRNA reversed the inhibitory effect of diosmetin on IL-1ß-induced degradation of ECM proteins and inflammatory factors in cultured chondrocytes. In the DMM-induced model of OA, diosmetin alleviated cartilage degeneration and decreased the Osteoarthritis Research Society International score. C: ONCLUSIONS: Diosmetin ameliorates expression of inflammation biomarkers and ECM macromolecules degradation in cultured murine chondrocytes via inactivation of NF-κB signaling by activating Nrf2/HO-1 signaling pathway.

Three-Dimensional Vanadium and Nitrogen Dual-Doped Ti3C2 Film with Ultra-High Specific Capacitance and High Volumetric Energy Density for Zinc-Ion Hybrid Capacitors.

Zinc-ion hybrid capacitors (ZICs) can achieve high energy and power density, ultralong cycle life, and a wide operating voltage window, and they are widely used in wearable devices, portable electronics devices, and other energy storage fields. The design of advanced ZICs with high specific capacity and energy density remains a challenge. In this work, a novel kind of V, N dual-doped Ti3C2 film with a three-dimensional (3D) porous structure (3D V-, N-Ti3C2) based on Zn-ion pre-intercalation can be fabricated via a simple synthetic process. The stable 3D structure and heteroatom doping provide abundant ion transport channels and numerous surface active sites. The prepared 3D V-, N-Ti3C2 film can deliver unexpectedly high specific capacitance of 855 F g-1 (309 mAh g-1) and demonstrates 95.26% capacitance retention after 5000 charge/discharge cycles. In addition, the energy storage mechanism of 3D V-, N-Ti3C2 electrodes is the chemical adsorption of H+/Zn2+, which is confirmed by ex situ XRD and ex situ XPS. ZIC full cells with a competitive energy density (103 Wh kg-1) consist of a 3D V-, N-Ti3C2 cathode and a zinc foil anode. The impressive results provide a feasible strategy for developing high-performance MXene-based energy storage devices in various energy-related fields.