Effects of silencing hsa_circ_0015326 on proliferation, migration, invasion, and apoptosis of epithelial ovarian cancer cells.

Although the treatment of ovarian cancer has made great progress, there are still many patients who are not timely detected and given targeted therapy due to unknown pathogenesis. Recent studies have found that hsa_circ_0015326 is upregulated in ovarian cancer and is involved in the proliferation, invasion, and migration of ovarian cancer cells. However, whether hsa_circ_0015326 can be used as a new target of ovarian cancer needs further investigation. Therefore, the effect of hsa_circ_0015326 on epithelial ovarian cancer was investigated in this study. At first, si-hsa_circ_0015326 lentivirus was transfected into epithelial ovarian cancer cells. Then real-time fluorescence quantitative PCR (qRT-PCR) was used to detect hsa_circ_0015326 level. The proliferation of ovarian cancer cells was detected by CCK-8 assay. The horizontal and vertical migration abilities of the cells were detected by wound-healing assay and Transwell assay, respectively. Transwell assay was also used to determine the invasion rate. As for the apoptosis rate, it was assessed by flow cytometry. As a result, the expression level of hsa_circ_0015326 in A2780 and SKOV3 was found to be higher than that in IOSE-80. However, after transfecting si-hsa_circ_0015326 and si-NC into the cells, the proliferation, migration, and invasion abilities of A2780 and SKOV3 cells in the si-hsa_circ_0015326 group were significantly reduced in comparison to those in the si-NC and mock groups, while their apoptosis rates were elevated. Collectively, silencing hsa_circ_0015326 bears the capability of inhibiting the proliferation, migration, and invasion of ovarian cancer cells while increasing apoptosis rate. It can be concluded that hsa_circ_0015326 promotes the malignant biological activities of epithelial ovarian cancer cells.

Positive association between chlorinated paraffins and the risk of allergic diseases in children and adolescents.

Contaminants may induce immune response polarization, leading to immune diseases, such as allergic diseases. Evidence concerning the effects of chlorinated paraffins (CPs), an emerging persistent organic pollutant, on immune system is scarce, particularly for epidemiological evidence. This study explores the association between CPs exposure and allergic diseases (allergic rhinitis, atopic eczema, and allergic conjunctivitis) in children and adolescents in the Pearl River Delta (PRD) in China. Herein, 131,304 children and adolescents from primary and secondary schools in the PRD were included and completed the questionnaire survey. The particulate matter (PM) samples were collected in the PRD and the PM2.5-bound CP concentrations were analyzed. In the multivarious adjustment mixed effect model (MEM), an IQR increase in ∑CPs was significantly associated with allergic diseases (rhinitis, eczema, and conjunctivitis) with the estimated odds ratios (ORs) for 1.11 (95% CI: 1.10, 1.13), 1.17 (95% CI: 1.15, 1.19), and 1.82 (95% CI: 1.76, 1.88), respectively. Interaction analysis indicated that overweight and obese individuals might have greater risk. Similar effect estimates were observed in several sensitivity analyses. This study provided epidemiological evidence on the immunotoxicity of CPs. More studies to confirm our findings and investigate mechanisms are needed.

Aflibercept combined with triamcinolone acetonide in the treatment of diabetic macular edema: optical coherence tomography and optical coherence tomography angiography.

AIM: To analyze the relationship between optical coherence tomography (OCT) and OCT angiography (OCTA) imaging in patients with diabetic macular edema (DME) who are treated with a combination of aflibercept and triamcinolone acetonide (TA). METHODS: A total of 76 eyes newly diagnosed DME were included in this study. They were randomly assigned to receive either aflibercept or a combination of aflibercept and TA. Injections once a month for a total of three injections. Central macular thickness (CMT), number of hyperreflective foci (HRF), height of subretinal fluid (SRF), and area of foveal avascular zone (FAZ) were evaluated using OCT and OCTA at baseline and after each monthly treatment. RESULTS: Both groups showed improvement in best corrected visual acuity (BCVA) and reduction in macular edema after treatment, and the difference in BCVA between the two groups was statistically significant after each treatment (P<0.05). The difference in CMT between the two groups was statistically significant after the first two injections (P<0.01), but not after the third injection (P=0.875). The number of HRF (1mo: 7.41±8.25 vs 10.86±7.22, P=0.027; 2mo: 5.33±6.13 vs 9.12±8.61, P=0.034; 3mo: 3.58±3.00 vs 6.37±5.97, P=0.007) and height of SRF (1mo: 82.39±39.12 vs 105.77±42.26 µm, P=0.011; 2mo: 36.84±10.02 vs 83.59±37.78 µm, P<0.01; 3mo: 11.57±3.29 vs 45.43±12.60 µm, P<0.01) in combined group were statistically significant less than aflibercept group after each injection, while the area of FAZ showed no significant change before and after treatment in both groups. CONCLUSION: The combination therapy of aflibercept and TA shows more significant effects on DME eyes with decreased HRF and SRF. However, both aflibercept and combination therapy show no significant change in the area of FAZ.

Characteristics of gut microbiota and its correlation with hs-CRP and somatic symptoms in first-episode treatment-naive major depressive disorder.

OBJECTIVE: Most patients with major depressive disorder (MDD) have somatic symptoms, but little studies pay attention in the microbial-inflammatory mechanisms of these somatic symptoms. Our study aimed to investigate alterations in gut microbiota and its correlation with inflammatory marker levels and somatic symptoms in first-episode treatment-naive MDD. METHODS: Subjects contained 160 MDD patients and 101 healthy controls (HCs). MDD patients were divided into MDD with somatic symptoms group (MDDS) and MDD without somatic symptoms group (MDDN) based on Somatic Self-rating Scale (SSS). 16S ribosomal RNA sequencing were performed to analyze the composition of the fecal microbiota. The inflammatory factors were measured using enzyme linked immunosorbent assay (ELISA). Correlation among the altered gut microbiota, inflammatory factor and severity of clinical symptoms were analysized. RESULTS: Relative to HCs, MDD patients had higher levels of high-sensitivity C-reactive protein (hs-CRP) as well as disordered α-diversity and ß-diversity of gut microbiota. Linear discriminant effect size (LEfSe) analysis showed that MDD patients had higher proportions of Bifidobacterium, Blautia, Haemophilus and lower proportions of Bacteroides, Faecalibacterium, Roseburia, Dialister, Sutterella, Parabacteroides, Bordetella, and Phascolarctobacterium from the genus aspect. Furthermore, correlation analysis showed Bacteroides and Roseburia had negative correlations with the hs-CRP, HAMD-24, the total and factor scores of SSS in all participants. Further, compared with MDDN, the Pielous evenness was higher in MDDS. Random Forest (RF) analysis showed 20 most important genera discriminating MDD-S and MDDN, HCs. The ROC analysis showed that the AUC was 0.90 and 0.81 combining these genera respectively. CONCLUSION: Our study manifested MDD patients showed disordered gut microbiota and elevated hs-CRP levels, and altered gut microbiota was closely associated with hs-CRP, depressive symptoms, and somatic symptoms.

CD146, a therapeutic target involved in cell plasticity.

Since its identification as a marker for advanced melanoma in the 1980s, CD146 has been found to have multiple functions in both physiological and pathological processes, including embryonic development, tissue repair and regeneration, tumor progression, fibrosis disease, and inflammations. Subsequent research has revealed that CD146 is involved in various signaling pathways as a receptor or co-receptor in these processes. This correlation between CD146 and multiple diseases has sparked interest in its potential applications in diagnosis, prognosis, and targeted therapy. To better comprehend the versatile roles of CD146, we have summarized its research history and synthesized findings from numerous reports, proposing that cell plasticity serves as the underlying mechanism through which CD146 contributes to development, regeneration, and various diseases. Targeting CD146 would consequently halt cell state shifting during the onset and progression of these related diseases. Therefore, the development of therapy targeting CD146 holds significant practical value.

Toosendanin inhibits T-cell proliferation through the P38 MAPK signalling pathway.

In recent years, immunosuppressants have shown significant success in the treatment of autoimmune diseases. Therefore, there is an urgent need to develop additional immunosuppressants that offer more options for patients. Toosendanin has been shown to have immunosuppressive activity in vitro as well as effects on autoimmune hepatitis (AIH) in vivo. Toosendanin did not induce apoptosis in activated T-cells and affect the survival rate of naive T-cells. Toosendanin did not affect the expression of CD25 or secretion of IL-2 by activated T-cells, and not affect the expression of IL-4 and INF-γ. Toosendanin did not affect the phosphorylation of STAT5, ERK, AKT, P70S6K. However, toosendanin inhibited proliferation of anti-CD3/anti-CD28 mAbs-activated T-cells with IC50 of (10 ± 2.02) nM. Toosendanin arrested the cell cycle in the G0/G1 phase, significantly inhibited IL-6 and IL-17A secretion, promoted IL-10 expression, and inhibited the P38 MAPK pathway. Finally, toosendanin significantly alleviated ConA-induced AIH in mice. In Summary, toosendanin exhibited immunosuppressive activity in vivo and in vitro. Toosendanin inhibits the proliferation of activated T-cells through the P38 MAPK signalling pathway, significantly suppresses the expression of inflammatory factors, enhances the expression of anti-inflammatory factors, and effectively alleviates ConA-induced AIH in mice, suggesting that toosendanin may be a lead compound for the development of novel immunomodulatory agents with improved efficacy and reduced toxicity.

Molecular Regulatory Mechanism of Nano-Se Against Copper-Induced Spermatogenesis Disorder.

Selenium nanoparticle (Nano-Se) is a new type of selenium supplement, which can improve the deficiency of traditional selenium supplements and maintain its physiological activity. Due to industrial pollution and irrational use in agriculture, Cu overexposure often occurs in animals and humans. In this study, Nano-Se alleviated CuSO4-induced testicular Cu accumulation, serum testosterone level decrease, testicular structural damage, and decrease in sperm quality. Meanwhile, Nano-Se reduced the ROS content in mice testis and enhanced the activities of T-AOC, GSH, SOD, and CAT compared with CuSO4 group. Furthermore, Nano-Se alleviated CuSO4-induced apoptosis by increasing the protein expression of Cleaved-Caspase-3, Cleaved-Caspase-9, Cleaved-Caspase-12, and Bax/Bcl-2 compared with CuSO4 group. At the same time, Nano-Se reversed CuSO4-induced increase of γ-H2AX protein expression in mice testis. In conclusion, this study confirmed that Nano-Se could alleviate oxidative stress, apoptosis, and DNA damage in the testis of mice with Cu excess, thereby protecting the spermatogenesis disorder induced by Cu.

Mechanically Robust, Durable, and Multifunctional Hyper-Crosslinked Elastomer Based on Metal-Organic-Cluster Crosslinker: The Role of Topological Structure.

Polymer materials formed by conventional metal-ligand bonds have very low branch functionality, the crosslinker of such polymer usually consists of 2-4 polymer chains and a single metal ion. Thus, these materials are weak, soft, humidity-sensitive, and unable to withstand their shape under long-term service. In this work, a new hyperbranched metal-organic cluster (MOC) crosslinker containing up to 16 vinyl groups is prepared by a straightforward coordination reaction. Compared with the current typical synthesis of metal-organic cages (MOCs) or metal-organic-polyhedra (MOP) crosslinkers with complex operations and low yield, the preparation of the MOC is simple and gram-scale. Thus, MOC can serve as a high-connectivity crosslinker to construct hyper-crosslinked polymer networks. The as-prepared elastomer exhibits mechanical robustness, creep-resistance, and humidity-stability. Besides, the elastomer possesses self-healing and recyclability at mild condition as well as fluorescence stability. These impressive comprehensive properties are proven to originate from the hyper-crosslinked topological structure and microphase-separated morphology. The MOC-driven hyper-crosslinked elastomers provide a new solution for the construction of mechanically robust, durable, and multifunctional polymers.

Metal-Coordinated Covalent Organic Frameworks as Advanced Bifunctional Hosts for Both Sulfur Cathodes and Lithium Anodes in Lithium-Sulfur Batteries.

The shuttling of polysulfides on the cathode and the uncontrollable growth of lithium dendrites on the anode have restricted the practical application of lithium-sulfur (Li-S) batteries. In this study, a metal-coordinated 3D covalent organic framework (COF) with a homogeneous distribution of nickel-bis(dithiolene) and N-rich triazine centers (namely, NiS4-TAPT) was designed and synthesized, which can serve as bifunctional hosts for both sulfur cathodes and lithium anodes in Li-S batteries. The abundant Ni centers and N-sites in NiS4-TAPT can greatly enhance the adsorption and conversion of the polysulfides. Meanwhile, the presence of Ni-bis(dithiolene) centers enables uniform Li nucleation at the Li anode, thereby suppressing the growth of Li dendrites. This work demonstrated the effectiveness of integrating catalytic and adsorption sites to optimize the chemical interactions between host materials and redox-active intermediates, potentially facilitating the rational design of metal-coordinated COF materials for high-performance secondary batteries.

Mechanically Adaptive Polymers Constructed from Dynamic Coordination Equilibria.

Designing materials capable of adapting their mechanical properties in response to external stimuli is the key to preventing failure and extending their service life. However, existing mechanically adaptive polymers are hindered by limitations such as inadequate load-bearing capacity, difficulty in achieving reversible changes, high cost, and a lack of multiple responsiveness. Herein, we address these challenges using dynamic coordination bonds. A new type of mechanically adaptive material with both rate- and temperature-responsiveness was developed. Owing to the stimuli-responsiveness of the coordination equilibria, the prepared polymers, PBMBD-Fe and PBMBD-Co, exhibit mechanically adaptive properties, including temperature-sensitive strength modulation and rate-dependent impact hardening. Benefitting from the dynamic nature of the coordination bonds, the polymers exhibited impressive energy dissipation, damping capacity (loss factors of 1.15 and 2.09 at 1.0 Hz), self-healing, and 3D printing abilities, offering durable and customizable impact resistance and protective performance. The development of impact-resistant materials with comprehensive properties has potential applications in the sustainable and intelligent protection fields.

Reversible single-crystal-to-single-crystal transition in Gd(III) metal-organic frameworks induced by heat and solvents with a significant magnetocaloric effect.

The design and synthesis of a Gd(III) metal-organic framework with the formula [Gd4(BTDI)3(DMF)4]n (JXUST-40, H4BTDI = 5,5'-(benzo[c][1,2,5]thiadiazole-4,7-diyl)diisophthalic acid) are reported hererin. Interestingly, a reversible single-crystal-to-single-crystal transition between JXUST-40 and {[Gd4(BTDI)3(H2O)4]·6H2O}n (JXUST-40a) was achieved under the stimulation of heat and solvents. Both JXUST-40 and JXUST-40a exhibited good stability when soaked in common solvents and aqueous solutions with pH values of 1-12. Magnetic studies showed that JXUST-40a has a larger magnetocaloric effect with -ΔSmaxm = 26.65 J kg-1 K-1 at 2 K and 7 T than JXUST-40 due to its larger magnetic density. Structural analyses indicated that the coordinated solvent molecules play a crucial role in the coordination environment around the Gd(III) ions and the change in the framework, ultimately leading to the changes in the pore size and magnetism between JXUST-40 and JXUST-40a. In addition, both isomorphic [Dy4(BTDI)3(DMF)4]n (JXUST-41) and {[Dy4(BTDI)3(H2O)4]·6H2O}n (JXUST-41a) displayed slow magnetic relaxation behaviour.

Comparative analysis of Deinagkistrodon acutus venom from Taiwan and China utilizing chromatographic, electrophoretic, and bioinformatic approaches, along with ELISA employing a monospecific antivenom.

Deinagkistrodon acutus is a medically important pitviper inhabiting mainly South China and Taiwan. The hemorrhagic effects of its envenoming are compatible to its venom, which is abundant in metalloproteases (svMPs) and C-type lectin-like proteins. In this study, we investigated geographic variations in the venom of D. acutus collected from Taiwan and four Mainland Chinese provinces: Fujian, Jiangxi, Anhui, and Hunan. The variations were assessed through high-performance liquid chromatography, non-metric multidimensional scaling analysis, gel electrophoresis, and enzyme-linked immunosorbent assay (ELISA) with a monospecific antivenom (DaMAV) generated against the Taiwanese D. acutus venom, and discussed based on venom-protein sequences in databases and literature related to D. acutus venom. Additionally, the cross-reactivity of DaMAV against Crotalus horridus and Calloselasma rhodostoma venoms was investigated. We noted differential abundances of D. acutus venom metalloproteases, C-type lectin-like proteins, and phospholipase A2, along with point mutations and selective expression of serine protease isoforms. The ELISA results revealed that the venom from Taiwan was more reactive toward Taiwanese DaMAV than the four Mainland Chinese venoms, consistent with chromatographic profile differences, whereas C. horridus venom presented moderate cross-reactivity with DaMAV. The observed immunoreactivities of these venom with DaMAV can be attributed to the high prevalence of their PIII-svMPs, which are the dominant antigens, and the conservation of PIII-svMP epitopes.

Insomnia among coronavirus disease 2019 survivors: A single-center cross-sectional study.

Since the coronavirus disease 2019 (COVID-19) epidemic, insomnia has become one of the longer COVID-19 symptoms. This study aimed to investigate insomnia among COVID-19 survivors and explore the occurrence and influencing factors of insomnia. A cross-sectional study was performed from December 2022 to February 2023 through an online questionnaire star survey with 8 questions. The insomnia severity index scale (ISI) was used to assess the severity of insomnia. Univariate analysis was used to analyze the factors related to COVID-19 infection. A total of 564 participants (183 males and 381 females) were surveyed in the present study. The prevalence of insomnia was 63.12%. Among these insomnia patients, there were 202 (35.82%) with sub-threshold symptoms, 116 (20.57%) with moderate symptoms, and 38 (6.74%) with severe symptoms. Univariate analysis indicated that there were statistically significant differences in the prevalence of insomnia among COVID-19 survivors of different ages, occupations, and educational levels (P < .05). Of the 356 insomnia patients, 185 (51.97%) did not take any measures against insomnia, while those who took drugs only, physical exercise only, drugs and physical exercise, and other measures were 90 (25.28%), 42 (11.80%), 17 (4.78%), and 22 (6.18%), respectively. Additionally, of the 107 insomnia patients with drug therapy, 17 (15.89%) took estazolam, 16 (14.95%) took alprazolam, 39 (36.45%) took zopiclone, and 35 (32.71%) took other drugs to improve insomnia symptoms. The prevalence of insomnia symptoms remains high among COVID-19 survivors in China. Education level and occupation may be the influencing factors. Unfortunately, most patients with insomnia do not take corresponding treatment measures.

Sertoli-Leydig Cell Tumor as a Cause of Elevated 17-OH Progesterone.

Virilizing ovarian tumors are rare but a clinically important diagnosis in a patient presenting with hyperandrogenism. Workup of hyperandrogenism is challenging with a broad range of differentials, including adrenal and ovarian pathology, tumoral or nontumoral in nature. Baseline follicular-phase 17-hydroxyprogesterone (17OHP) measurement is part of the investigation algorithm, and elevated levels are often associated with nonclassic congenital adrenal hyperplasia (NCCAH), which can have its first presentation in adolescence or adulthood. This case describes a young adult woman of reproductive age presenting with menstrual irregularity, raised testosterone, and 17OHP. After extensive workup and serial follow-up, she was found to have a Sertoli-Leydig cell tumor of the left ovary and underwent successful laparoscopic salpingo-oophorectomy with normalization of her menstrual irregularity and biochemical resolution of her testosterone and 17OHP levels.

Effect of aflibercept combined with triamcinolone acetonide on aqueous humor growth factor and inflammatory mediators in diabetic macular edema.

AIM: To investigate the efficacy of aflibercept combined with sub-tenon injection of triamcinolone acetonide (TA) in treating diabetic macular edema (DME) and to examine changes in growth factors and inflammatory mediator levels in aqueous humor after injection. METHODS: Totally 67 DME patients (67 eyes) and 30 cataract patients (32 eyes) were enrolled as the DME group and the control group, respectively. The DME group was divided into the aflibercept group (34 cases) and the aflibercept combined with TA group (combined group, 33 cases). The aqueous humor of both groups was collected during the study period. The aqueous levels of vascular endothelial growth factor (VEGF), monocyte chemoattractant protein-1 (MCP-1), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-1ß (IL-1ß) were detected using a microsphere suspension array technology (Luminex 200TM). Aqueous cytokines, best-corrected visual acuity (BCVA), central macular thickness (CMT), and complications before and after treatment were compared between the aflibercept group and combined group. RESULTS: The concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly higher in the DME group than those of the control group (all P<0.01). After 1mo of surgery, the concentrations of VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor were significantly lower in the combined group than those of the aflibercept group (all P<0.01). The BCVA and CMT values of the two groups were statistically different after 1 and 2mo of treatment (P<0.01). However, the difference was not statistically significant after 3mo of treatment (P>0.05). CONCLUSION: The cytokines VEGF, MCP-1, IL-6, and IL-8 in the aqueous humor of DME patients are significantly increased. Aflibercept and aflibercept combined with TA have good efficacy in DME patients, can effectively reduce CMT, improve the patient's vision, and have high safety. Aflibercept combined with TA can quickly down-regulate the aqueous humor cytokines and help to relieve macular edema rapidly. However, the long-term efficacy is comparable to that of aflibercept alone.

Copper Promotes LPS-Induced Inflammation via the NF-кB Pathway in Bovine Macrophages.

Inflammation is a complex physiological process that enables the clearance of pathogens and repairing damaged tissues. Elevated serum copper concentration has been reported in cases of inflammation, but the role of copper in inflammatory responses remains unclear. This study used bovine macrophages to establish lipopolysaccharide (LPS)-induced inflammation model. There were five groups in the study: a group treated with LPS (100 ng/ml), a group treated with either copper chelator (tetrathiomolybdate, TTM) (20 µmol) or CuSO4 (25 µmol or 50 µmol) after LPS stimulation, and a control group. Copper concentrations increased in macrophages after the LPS treatment. TTM decreased mRNA expression of pro-inflammatory factors (IL-1ß, TNF-α, IL-6, iNOS, and COX-2), whereas copper supplement increased them. Compared to the control group, TLP4 and MyD88 protein levels were increased in the TTM and copper groups. However, TTM treatment decreased p-p65 and increased IкB-α while the copper supplement showed reversed results. In addition, the phagocytosis and migration of bovine macrophages decreased in the TTM treatment group while increased in the copper treatment groups. Results mentioned above indicated that copper could promote the LPS-induced inflammatory response in bovine macrophages, promote pro-inflammatory factors by activating the NF-кB pathway, and increase phagocytosis capacity and migration. Our study provides a possible targeted therapy for bovine inflammation.

Effect of the Novel Free Radical Scavenger 4'-Hydroxyl-2-Substituted Phenylnitronyl Nitroxide on Oxidative Stress, Mitochondrial Dysfunction and Apoptosis Induced by Cerebral Ischemia-Reperfusion in Rats.

Mitochondrial dysfunction, which results in the overproduction of oxygen free radicals, is a crucial mechanism underlying cerebral ischemia-reperfusion injury. 4'-Hydroxyl-2-substituted phenylnitronyl nitroxide (HPN), which is an antioxidant and free radical scavenger, can effectively scavenge oxygen free radicals, suggesting its potential as a protective agent against cerebral ischemia-reperfusion injury. In this study, we investigated the effects of HPN on mitochondrial function and apoptosis following cerebral ischemia/reperfusion injury in rats. Healthy adult SD rats were chosen as the experimental subjects, and the rat ischemia/reperfusion injury model was generated using the modified Zea Longa method. The administration of HPN significantly enhanced the activity of endogenous antioxidant enzymes, such as superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT). Additionally, HPN effectively preserved the morphology and function of mitochondria, reduced the protein and gene expression of Caspase-3 and Bax, increased the protein and gene expression of Bcl-2, mitigated neuronal apoptosis, improved neurological deficits, and decreased the volume of cerebral infarction. Of interest, the protective effect on brain tissue was more evident with increasing doses of HPN. These findings indicate that HPN can serve as an effective protective agent against cerebral ischemia-reperfusion injury.