Sustained response to anlotinib in advanced pancreatic neuroendocrine carcinoma: A case report.

Pancreatic neuroendocrine carcinoma (pNEC) is a type of pancreatic neuroendocrine neoplasm with a poor prognosis, and patients with metastatic pNEC have a survival time of only 8-12 months. The treatment options for pNEC are minimal, and the prognosis is unfavorable. The present study reports the case of a 56-year-old male who was diagnosed with advanced pNEC with bone metastases in June 2018. The patient was treated with oral anlotinib after eight cycles of first-line etoposide + cisplatin (EP) chemotherapy until July 2022. The adverse events that occurred during the treatment period were resolved with symptomatic management or drug dose reduction. At the time of writing this report, the patient's survival time was almost 60 months, which is rare for patients with pNEC. This case report suggests that patients with pNEC treated with first-line EP regimen chemotherapy may have a sustained response to anlotinib.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/SHOC2 feedback loop.

OBJECTIVE: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. METHODS: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. RESULTS: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. CONCLUSION: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

circCPA4 induces malignant behaviors of prostate cancer via miR-491-5p/ SHOC2 feedback loop

ABSTRACT Objective: circCPA4 has been defined to be an oncogenic gene. This study examined whether circCPA4 regulates Prostate Cancer (PC) development and revealed its molecular mechanism. Methods: PC tissues and PC cell lines were collected, in which circCPA4/miR-491-5p/SHOC2 levels were evaluated by RT-qPCR and immunoblot. Colony formation assay and EdU assay assessed cell proliferation, flow cytometry measured apoptosis, and Transwell assessed invasion and migration. Ki-67, cleaved caspase-3, E-cadherin, and N-cadherin were evaluated by immunoblot. Based on the luciferase reporter assay and RIP assay the authors investigated the targeting relationship between circCPA4/miR-491-5p/SHOC2. The effect of circCPA4 on tumor growth was evaluated by xenotransplantation in nude mice. Results: circCPA4 and SHOC2 levels were abundant while miR-491-5p expression was low in PC. Loss of circCPA4 decreased the proliferation and EdU-positive rate of PC cells, enhanced apoptosis, and inhibited invasion, migration, and EMT. Upregulation of circCPA4 forced the malignant behaviors of PC cells, and this promotion could be abolished when miR-491-5p was overexpressed or SHOC2 was silenced. CircCAP4 competitively decoyed miR-491-5p mediating SHOC2 expression. circCAP4 suppression inhibited PC tumor growth. Conclusion: circCAP4 acts as a novel oncogenic factor in PC, accelerating the malignant behavior of PC cells via miR-491-5p/SHOC2 interaction. This novel ceRNA axis may be a potential target for PC drug development and targeted therapy in the future.

Magnetic particle-based chemiluminescence immunoassay for serum human heart-type fatty acid binding protein measurement.

OBJECTIVES: Human heart-type fatty acid binding protein (HFABP) is a biomarker for diagnosis, risk assessment, and prognosis of acute myocardial infarction, and we aimed to establish an immunoassay for HFABP quantitation. METHODS: Human HFABP monoclonal antibodies (mAbs) were developed, evaluated by enzyme-linked immunosorbent assay, and a chemiluminescence enzyme immunoassay (CLEIA) generated. Analytical performance of the CLEIA was evaluated by measuring serum HFABP. RESULTS: The prokaryotically expressed rHFABP was purified and four anti-HFABP mAbs with superior detection performance were obtained after immunizing BALB/c mice. MAbs 2B8 and 6B3 were selected as respective capture and detection antibodies for HFABP measurement by CLEIA (detection range, 0.01-128 µg/L). Results using the CLEIA showed excellent correlation (r, 0.9622) and the correlation coefficient was 0.9809 (P < 0.05) by the Tukey test statistical analysis with those of latex-enhanced immunoturbidimetry in hospitals. CONCLUSION: Our mAbs and CLEIA for HFABP detection represent new diagnostic tools for measurement of human serum HFABP.

Honokiol induces apoptosis-like death in Cryptocaryon irritans Tomont.

BACKGROUND: Cryptocaryon irritans, a common parasite in tropical and subtropical marine teleost fish, has caused serious harm to the marine aquaculture industry. Honokiol was proven to induce C. irritans tomont cytoplasm shrinkage and death in our previous study, but the mechanism by which it works remains unknown. METHODS: In this study, the changes of apoptotic morphology and apoptotic ratio were detected by microscopic observation and AnnexinV-FITC/PI staining. The effects of honokiol on intracellular calcium ([Ca2+]i) concentration, mitochondrial membrane potential (ΔΨm), reactive oxygen species (ROS), quantity of DNA fragmentations (QDF) and caspase activities were detected by Fluo-3 staining, JC-1 staining, DCFH-DA staining, Tunel method and caspase activity assay kit. The effects of honokiol on mRNA expression levels of 61 apoptosis-related genes in tomonts of C. irritans were detected by real-time PCR. RESULTS: The results of the study on the effects of honokiol concentration on C. irritans tomont apoptosis-like death showed that the highest levels of prophase apoptosis-like death rate (PADR), [Ca2+]i concentration, ROS, the activities of caspase-3/9 and the lowest necrosis ratio (NER) were obtained at a concentration of 1 µg/ml, which was considered the most suitable for inducing C. irritans tomont apoptosis-like death. When C. irritans tomonts were treated with 1 µg/ml honokiol, the [Ca2+]i concentration began to increase significantly at 1 h. Following this, the ROS, QDF and activities of caspase-3/9 began to increase significantly, and the ΔΨm began to decrease significantly at 2 h; the highest PADR was obtained at 4 h. The mRNA expression of 14 genes was significantly upregulated during honokiol treatment. Of these genes, itpr2, capn1, mc, actg1, actb, parp2, traf2 and fos were enriched in the pathway related to apoptosis induced by endoplasmic reticulum (ER) stress. CONCLUSIONS: This article shows that honokiol can induce C. irritans tomont apoptosis-like death. These results suggest that honokiol may disrupt [Ca2+]i homeostasis in ER and then induce C. irritans tomont apoptosis-like death by caspase cascade or mitochondrial pathway, which might represent a novel therapeutic intervention for C. irritans infection.

Nasal and Sellar Anatomic Variations in Pituitary-Dependent Cushing Disease.

OBJECTIVE: Adrenocorticotrophic hormone excessive secretion in pituitary-dependent Cushing disease (CD) patients may lead to anatomic variations of the nasal-sphenoidal corridor as a result of hormone-induced abnormal soft tissue change. However, there is still a lack of data on anatomic dimensions in CD patients. In this study, magnetic resonance images were analyzed to determine the anatomic variations of the nasal cavity and sphenoid sinus in CD patients. METHODS: A retrospective radiographic analysis was conducted on CD patients undergoing endonasal transsphenoidal surgery as primary treatment between January 2013 and December 2017. A total of 97 CD patients and 100 controls were included. The nasal and sphenoidal anatomic dimensions of CD patients were compared with the control group. RESULTS: Both sides of nasal cavity height, middle nasal meatus width, and inferior nasal meatus width in CD patients were narrower than that of controls. When compared with controls, the ratio of the middle turbinate to middle nasal meatus and the ratio of inferior turbinate to inferior nasal meatus was found to increase on both sides in CD patients. Intercarotid distance of CD patients was shorter than that of controls. The most prevalent pneumatization pattern of CD patients was postsellar, followed by sellar, presellar, and conchal. CONCLUSIONS: Cushing disease patients have nasal and sphenoidal anatomic variations affecting the endonasal transsphenoidal surgical corridor, especially the shorter intercarotid distance. The neurosurgeon should be aware of these anatomic variations, and adapt surgical techniques and optimal approaches to reach the sella safely.

Preparation of monoclonal antibodies against Epstein-Barr virus glycoprotein 350.

Epstein-Barr virus (EBV) is the first identified human oncogenic herpesvirus infecting over 90% of the adults worldwide. However, the safe and effective prophylactic vaccine has not been licensed. The major glycoprotein 350 (gp350) on the EBV envelope is the main target for neutralizing antibodies, and gp350 (aa15-320) was used for the development of monoclonal antibodies in present study. The purified recombinant gp35015-320aa with an estimated molecular weight of 50 kDa was used to immunize six-week-old BALB/c mice, and the hybridoma cell lines that stably secreted monoclonal antibodies (mAbs) were obtained. The ability of developed mAbs for capturing and neutralizing EBV was evaluated, and mAb 4E1 presented better performance to block the infection of EBV in cell line Hone-1. The mAb 4E1 recognized the epitope. Its sequence of variable region genes (VH and VL) presented a unique identity which hadn't been reported. The developed mAbs might benefit the antiviral therapy and immunologic diagnosis for EBV infection.

Inhibiting thioredoxin glutathione reductase is a promising approach to controlling Cryptocaryon irritans infection in fish.

Marine cultured fish often suffer from Cryptocaryon irritans infection, which causes enormous mortality. C. irritans is resistant to oxidative damage induced by zinc. To develop an effective drug to control the parasite, a putative thioredoxin glutathione reductase (CiTGR) from C. irritans was cloned and characterized. CiTGR was designed as a target to screen for inhibitors by molecular docking. The selected inhibitors were tested both in vitro and in vivo. The results showed that CiTGR is located in the nucleus of the parasite, possesses a common pyridine-oxidoreductases redox active center, and lacks a glutaredoxin active site. Recombinant CiTGR exhibited high TrxR activity but low glutathione reductase activity. Shogaol was found to significantly suppress TrxR activity and enhance toxicity of zinc on C. irritans (P < 0.05). The abundance of C. irritans on the fish body decreased significantly after oral administration of shogaol (P < 0.05). These results implied that CiTGR could be used to screen for drugs that weaken the resistance of C. irritans to oxidative stress, which is critical for controlling the parasite in fish. This paper deepens the understanding of the interaction between ciliated parasites and oxidative stress.

Supplementing a specific synbiotic suppressed the incidence of AOM/DSS-induced colorectal cancer in mice.

In this study, we evaluated the effect of a specific synbiotic on CAC (AOM/DSS-induced colitis-associated cancer). We confirmed that the synbiotic intervention was able to protect the intestinal barrier and inhibit CAC occurrence via upregulating tight junction proteins and anti-inflammatory cytokines, and downregulating pro-inflammatory cytokines. Moreover, the synbiotic significantly improved the disorder of the colonic microbiota of CAC mice, promoted the formation of SCFAs and the production of secondary bile acids, and alleviated the accumulation of primary bile acids in the CAC mice. Meanwhile, the synbiotic could significantly inhibit the abnormal activation of the intestinal Wnt/ß-catenin signaling pathway significantly related to IL-23. In a word, the synbiotic can inhibit the occurrence and development of colorectal tumors and it may be a functional food to prevent inflammation-related colon tumors, and the research also provided a theoretical basis for improving the intestinal microecological environment through diet therapy.

Correlation Study between Quality and Sensory Characteristics of Kelp Paste by Aspergillus oryzae and Aspergillus niger during Fermentation.

In order to clarify the relationship between quality and sensory characteristics of kelp paste during fermentation, this study analyzed the quality and sensory characteristics of kelp paste through physicochemical indexes, nutritional components, electronic nose and electronic tongue. The results showed that with the extension of fermentation time, the contents of amino nitrogen, total acid, ammonium salt and ash increased gradually, while the pH value, moisture, fat, protein and carbohydrate decreased gradually. Short-chain alkanes such as nitrogen oxides and methane were the main causes of odor. Freshness, salinity and richness were the main indexes of kelp paste taste. Many quality indexes, such as amino nitrogen and protein, were significantly related to the odor sensor, which can better reflect the odor produced in the fermentation process of kelp paste. There was a significant correlation between quality indicators and important taste indicators such as umami, richness and salty taste, which can better reflect the taste of kelp paste during fermentation. To sum up, there was a significant correlation between the quality characteristics and sensory quality of kelp paste, so the relationship between quality characteristics and sensory characteristics in kelp paste can be clarified.

Effects of Porphyra haitanensis polysaccharides on gelatinization and gelatinization kinetics of starches with different crystal types.

The effects of Porphyra haitanensis polysaccharide (PHP) on the gelatinization and gelatinization kinetics of corn starch (CS), potato starch (PS) and lotus seed starch (LS) were studied. The gelatinization, rheological and thermal enthalpy properties of the samples were measured by a rapid viscosity analyzer (RVA), a rheometer, and a differential scanning calorimeter (DSC), respectively. And the kinetic equations were further established. RVA confirmed that the addition of 0.4 %, 0.8 % and 1.2 % PHP elevated the gelatinization viscosity of CS and LS but decreased that of the PS, and also elevated the thermal balance of CS, PS, and LS, especially PS (The breakdown viscosity was decreased to 363.00 ± 6.08, 370.00 ± 1.15, and 362.00 ± 0.58, respectively). And the rheometer indicated that the addition of 0.4 %, 0.8 % and 1.2 % PHP improved the apparent viscosity of CS, PS and LS, especially PS (The consistency coefficient was increased to 18.26 ± 0.02, 21.71 ± 0.04, and 23.26 ± 0.01, respectively). Eventually, DSC displayed that the addition of 0.4 %, 0.8 % and 1.2 % PHP extended the gelatinization temperature and enthalpy of CS, PS, and LS, especially PS. Among them, the gelatinization temperature (63.40 ± 0.03, 70.26 ± 0.02 and 74.61 ± 0.01, respectively) and the gelatinization enthalpy (1.55 ± 0.01) of PS increased the most with 1.2 % PHP. Moreover, gelatinization kinetics displayed that the addition of 0.4 %, 0.8 % and 1.2 % PHP decreased the rate constants of CS, PS, and LS and accelerated the activation energies of CS (666.37 ± 4.23, 623.89 ± 4.21 and 558.39 ± 2.35, respectively) and PS (752.53 ± 4.13, 699.61 ± 3.78 and 662.15 ± 4.52, respectively) while reducing that of the LS (938.87 ± 3.38, 669.98 ± 4.61 and 491.48 ± 4.29, respectively). Therefore, the addition of PHP at all concentrations inhibited the gelatinization procedure of CS and PS but promoted that of the LS. This study provided a theoretical basis for the creation of new products based on PHP and starch.

Association between general anesthesia and contrast-induced encephalopathy after endovascular treatment on neurovascular diseases.

Objective: Contrast-induced encephalopathy (CIE) is a rare neurological complication that can occur in the context of various endovascular procedures. Although many potential risk factors for CIE have been reported, it is still unclear whether anesthesia is a risk factor for the occurrence of CIE. The goal of this study was to investigate the incidence of CIE in patients who underwent endovascular treatment under different anesthesia methods and anesthetics administration and to explore whether general anesthesia was a potential risk factor for CIE. Methods: We retrospectively reviewed available clinical data from 1,043 patients with neurovascular diseases undergoing endovascular treatment between June 2018 and June 2021 in our hospital. A propensity score-based matching strategy and logistic regression were used to analyze the association between anesthesia and the occurrence of CIE. Results: In this study, we implemented the embolization of intracranial aneurysm in 412 patients, stent implantation of extracranial artery stenosis in 346, stent implantation of intracranial artery stenosis in 187, embolization of cerebral arteriovenous malformation or dural arteriovenous fistula in 54, endovascular thrombectomy in 20, and other endovascular treatments in 24. A total of 370 patients (35.5%) received treatment under local anesthesia, while the remaining 673 (64.5%) underwent treatment under general anesthesia. In total, 14 patients were identified as CIE, resulting in a total incidence rate of 1.34%. After propensity score-based matching of anesthesia methods, the occurrence of CIE was significantly different between the general anesthesia and local anesthesia group (P = 0.007). After propensity score-based matching of CIE, the anesthesia methods were significantly different between the two groups. Pearson contingency coefficients and logistic regression showed a significant correlation between general anesthesia and the risk of CIE. Conclusion: General anesthesia might be a risk factor for CIE, and propofol might be associated with the increased occurrence of CIE.

Characterization of genotype IV hepatitis E virus-like particles expressed in E.coli.

HEV (Hepatitis E virus) is an infectious disease transmitted between humans and animals, which poses a severe threat to the biological safety and property throughout the world. The disease is especially severe in patients with potential liver cirrhosis and women during pregnancy. There is no specific and thorough HEV treatment at present. The development of hepatitis E virus vaccine is vital to the prevention of viral hepatitis worldwide. Since HEV cannot grow adequately in vitro, vaccine developed by devitalized virus particles does not work. Exploration of HEV-like structures is essential for the development of functional vaccines against HEV infection. ORF2 encodes the structural proteins of HEV, some of which can automatically assemble into virus-like particles (VLP) in this experiment, the recombinant capsid protein p27 was expressed in E. coli and the VLP formed by p27 was used to immunize mice. The results showed that the VLP formed by recombinant P27 had similar particle size to that of HEV; the immune dose produced by p27 was positively correlated with the immune effect. Compared with other genetic engineering subunit vaccines, P27 protein has a better application prospect.

Differential Expressions of ADAM28 and ADAMTSL3 in Gingival Tissue of Patients with Periodontitis.

The modulation of gene expression via DNA methylation modifications is relevant to the pathogenesis of periodontitis. This study aimed at identifying novel biomarkers in gingival tissues from periodontitis by integrally analyzing methylation profiles and gene expression data. Differential gene expressions (DGEs) of dataset GSE106090 were obtained from the Gene Expression Omnibus (GEO) database for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. DNA methylation DGEs (DM-DGEs) were analyzed from dataset GSE173082. After integrating these two datasets, expressions of common genes were validated in gingival tissues from healthy controls and periodontitis patients by real-time quantitative polymerase chain reaction (RT-qPCR) and western blotting. GO analysis of 748 upregulated and 847 downregulated DEGs from the GSE106090 dataset revealed that immune response-regulating signaling pathway, cell-cell junction and signaling receptor activator activity as the top enriched biological process (BP), cellular component (CC) and molecular function (MF), respectively. DEGs were mainly enriched in cytokine-cytokine receptor interaction, Ras signaling pathway, and chemokine signaling pathway. There was one up-regulated mRNA with hypo-methylated gene [ADAM28 (a disintegrin and metalloproteinase 28)] and one down-regulated mRNA with hyper-methylated gene [ADAMTSL3 (a disintegrin-like and metalloprotease domain with thrombospondin type I motifs-like-3)] after integrating GSE106090 and GSE173082 datasets. Increased ADAM28 expression was validated in gingival tissues from periodontitis patients as compared to the healthy controls with decreased ADAMTSL3 expression, which were correlated with disease stage. ADAM28 and ADAMTSL3 may act as novel biomarkers in gingival tissues from periodontitis by a comprehensive analysis of bioinformatics methods and executed validation.

Reoperation for Recurrent and Persistent Cushing's Disease without Visible MRI Findings.

PURPOSE: Transsphenoidal surgery is the first-line treatment for Cushing's disease (CD), even with negative preoperative magnetic resonance imaging (MRI) results. Some patients with persistent or recurring hypercortisolism have negative MRI findings after the initial surgery. We aimed to analyze the efficacy of repeat surgery in two groups of patients and determine if there is an association between positive MRI findings and early remission. PATIENTS AND METHODS: Clinical, imaging, and biochemical information of 42 patients who underwent repeat surgery by a single neurosurgeon between 2002 and 2021 was retrospectively analyzed. We compared the endocrinological, histopathological, and surgical outcomes before and after repeat surgery among 14 CD patients with negative MRI findings and 28 patients with positive MRI findings. RESULTS: Immediate remission was achieved in 29 patients (69.0%) who underwent repeat surgery. Among all patients, 28 (66.7%) had MRI findings consistent with solid lesions. There was no significant difference in remission rates between the recurrence and persistence groups (77.8% vs. 57.1%, odds ratio = 2.625, 95% confidence interval = 0.651 to 10.586). Patients in remission after repeat surgery were not associated with positive MRI findings (odds ratio = 3.667, 95% confidence interval = 0.920 to 14.622). CONCLUSIONS: In terms of recurrence, repeat surgery in patients with either positive or negative MRI findings showed reasonable remission rates. For persistent disease with positive MRI findings, repeat surgery is still an option; however, more solid evidence is needed to determine if negative MRI findings are predictors for failed reoperations for persistent hypercortisolism.

Glutathione metabolism in Cryptocaryon irritans involved in defense against oxidative stress induced by zinc ions.

BACKGROUND: Cryptocaryon irritans is a fatal parasite for marine teleosts and causes severe economic loss for aquaculture. Galvanized materials have shown efficacy in controlling this parasite infestation through the release of zinc ions to induce oxidative stress. METHODS: In this study, the resistance mechanism in C. irritans against oxidative stress induced by zinc ions was investigated. Untargeted metabolomics analysis was used to determine metabolic regulation in C. irritans in response to zinc ion treatment by the immersion of protomonts in ZnSO4 solution at a sublethal dose (20 µmol). Eight differential metabolites were selected to assess the efficacy of defense against zinc ion stimulation in protomonts of C. irritans. Furthermore, the mRNA relative levels of glutathione metabolism-associated enzymes were measured in protomonts following treatment with ZnSO4 solution at sublethal dose. RESULTS: The results showed that zinc ion exposure disrupted amino acid metabolism, carbohydrate metabolism, lipid metabolism, and nucleotide metabolism in C. irritans. Four antioxidants, namely ascorbate, S-hexyl-glutathione, syringic acid, and ubiquinone-1, were significantly increased in the Zn group (P < 0.01), while the glutathione metabolism pathway was enhanced. The encystment rate of C. irritans was significantly higher in the ascorbate and methionine treatment (P < 0.05) groups. Additionally, at 24 h post-zinc ion exposure, the relative mRNA level of glutathione reductase (GR) was increased significantly (P < 0.01). On the contrary, the relative mRNA levels of glutathione S-transferase (GT) and phospholipid-hydroperoxide glutathione peroxidase (GPx) were significantly decreased (P < 0.05), thus indicating that the generation of reduced glutathione was enhanced. CONCLUSIONS: These results revealed that glutathione metabolism in C. irritans contributes to oxidative stress resistance from zinc ions, and could be a potential drug target for controlling C. irritans infection.

The expression and clinical significance of miR-30b-3p and miR-125b-1-3p in patients with periodontitis.

OBJECTIVE: Periodontitis is a chronic inflammatory infectious disease caused by the deposition of dental plaque on the tooth surface, leading to adverse systemic consequences. Accumulating evidence shows that dysregulated microRNAs (miRNAs) are associated with the disease severity of periodontitis. Herein, we report two novel miRNAs, miR-30b-3p and miR-125b-1-3p, in the context of periodontitis and their relationships with disease severity of periodontitis. METHODS: The miRNA profiles of gingival crevicular fluid (GCF) samples were used to screen differentially expressed miRNAs (DEmiRNAs) between periodontitis patients and periodontally healthy individuals. Clinical human GCF samples were collected from 80 patients diagnosed with periodontitis (PD +) for the first time and 100 periodontally healthy individuals (PD-). The severity of periodontitis was categorized into mild/moderate (MPD) and severe (SPD) groups. The expressions of miR-30b-3p and miR-125b-1-3p were determined by quantitative real-time PCR. The levels of IL-1ß, IL-6, and TNF-α were determined by ELISA methods. RESULTS: We applied GEO2R bioinformatics tool to analyze the raw data of the GSE89081 dataset and identified miR-30b-3p (|logFC|= 1.987) and miR-125b-1-3p (|logFC|= 1.878) between periodontitis patients and periodontally healthy individuals. It was found that PPD, CAL, BOP, and the relative expression levels of miR-30b-3p and miR-125b-1-3p were all higher in the PD + group than the PD- group, in the SPD group than the MPD group (P < 0.05). The periodontitis patients with high-miR-30b-3p expression exhibited increased PPD, CAL, and BOP compared to those low-miR-30b-3p expression, while high-miR-125b-1-3p expression group showed significant differences on PPD and BOP from low-miR-125b-1-3p expression group (P < 0.05). Pearson correlation analysis demonstrated a significantly positive correlation between the levels of inflammatory cytokines, miR-30b-3p expression, and miR-125b-1-3p expression (P < 0.001). Results of ROC curves showed AUC of 0.878 and 0.927, sensitivity of 0.843 and 0.855, and specificity of 0.791 and 0.801, respectively, when miR-30b-3p and miR-125b-1-3p expression levels were used to diagnose periodontitis. CONCLUSION: These data unveiled that miR-30b-3p and miR-125b-1-3p expressions may be associated with the pathogenesis of periodontitis.

Skin transcriptomic analysis and immune-related gene expression of golden pompano (Trachinotus ovatus) after Amyloodinium ocellatum infection.

Amyloodiniosis is a severe disease of marine and brackish water fish caused by Amyloodinium ocellatum. Golden pompano (Trachinotus ovatus) is often repeatedly infected by A. ocellatum, leading to extensive mortality. However, little is known about the immune response mechanisms of the T. ovatus following reinfection with A. ocellatum. In this study, an extensive analysis at the transcriptome level of T. ovatus skin was carried out at 24 h post-infection by A. ocellatum. During the transcriptomic analysis, 1367 differentially expressed genes (DEGs) in the skin of T. ovatus under A. ocellatum infection and control conditions were obtained. In Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotated analyses, the DEGs were significantly enriched in the immune-related pathways. To better understand the immune-related gene expression dynamics, a quantitative reverse transcription-polymerase chain reaction (RT-qPCR) was used to assess the primary and secondary infection groups of T. ovatus at different stages (3 h, 12 h, 24 h, 48 h and, 72 h post-infection) of infection with A.ocellatum. The results showed that innate immunity-related genes [interleukin (IL-8), chemokine ligand 3 (CCL3), toll-like receptor 7 (TLR7), and G-type lysosome (LZM g)] and adaptive immunity-related gene [major histocompatibility complex (MHC) alpha antigen I and MHC alpha antigen II] expression levels in the primary and secondary infection groups were significantly increased compared to the control group. The expression of MHC I and MHC II was more rapidly upregulated in the secondary infection group compared with the primary infection group after A.ocellatum infection. However, no significant differences of A.ocellatum load were observed in primary and secondary infection groups. In addition, the serum of the primary infection group had significantly higher concentrations of triglyceride (TG), higher alanine transaminase (ALT), aspartate transaminase (AST), and lactate dehydrogenase (LDH) activities than the control group. This study contributes to understanding the defense mechanisms in fish skin against ectoparasite infection.

Single-Stage Endovascular Treatment of Severe Cranial Artery Stenosis Coexisted With Ipsilateral Distal Tandem Intracranial Aneurysm.

Objective: The coexistence of severe cranial artery stenosis and ipsilateral distal tandem intracranial aneurysm is an unusual phenomenon. Currently, there is no consensus to provide treatment guidelines for concomitant lesions. This study aims to evaluate the safety and effectiveness of single-stage endovascular treatment in patients under this special condition. Methods: We illustrated a case series of 10 patients with the coexistence of severe cranial artery stenosis and ipsilateral distal tandem intracranial aneurysm in our hospital. And a systematic PubMed search of English-language literature published between 1990 and 2021 was carried out using the keywords: "(carotid OR vertebral OR subclavian artery stenosis) AND (aneurysm) AND (coincident OR coexist OR concomitant OR simultaneous OR ipsilateral)." Clinical information, including age, gender of the patients, as well as symptoms (artery stenosis or aneurysm), localization of artery stenosis and aneurysm, treatment, and outcome, were collected and analyzed. Results: In the majority of the patients, symptoms were attributed to severe artery stenosis, and the coexisted lesions were located in the anterior circulation system. Most patients achieved an excellent clinical outcome, and no death was observed. No differences were found in a prognosis between single-stage or multiple-stage endovascular treatment. Conclusions: A single-stage endovascular procedure is technically feasible and effective to treat the coexistence of severe cranial artery stenosis and ipsilateral distal tandem intracranial aneurysm in the anterior circulation as well as in the posterior circulation.

High-mobility group box chromosomal protein-1 deletion alleviates osteoporosis in OVX rat model via suppressing the osteoclastogenesis and inflammation.

BACKGROUND: Osteoporosis is a skeletal metabolic disease that constitutes a great threaten to human health. However, there is currently no gold standard for its treatment. High-mobility group box chromosomal protein-1 (HMGB-1) has been reported to play an important role in various orthopedic diseases. Till now, its role in osteoporosis remains elusive. METHODS: Rats underwent ovariectomy (OVX) were used to construct a postmenopausal model of osteoporosis. Then, rats were divided into sham groups without OVX surgery, OVX model group, HMGB-1 knockdown (HMGB-1 KD) OVX model groups. The expression of HMGB1 was evaluated by qRT-PCR and western blotting. Subsequently, the changes of trabeculae were evaluated by micro-computed tomography (CT) assay. Skeletal necrosis and metabolism were further analyzed by hematoxylin-eosin (HE) staining, Alcian blue staining and Masson's trichrome staining. The contents of serum alkaline phosphatase (ALP) and osteocalcin were detected by ELISA assay. Expression of osteoclast-associated receptor (OSCAR) and tartrate-resistant acid phosphatase (TRAP) were determined to investigate the effects of HMGB-1 loss on osteoclastogenesis. RESULTS: Single HMGB-1 deletion exerted no significant effect on rat trabeculae, serum ALP and osteocalcin. Noticeably, HMGB1 knockdown dramatically ameliorated OVX-induced changes in above indexes. Trabeculae structures of OVX rats were sparse with disorder arrangement, which were greatly recovered after HMGB-1 deletion. Enhanced osteoclastogenesis was observed in OVX rats by increasing number of TRAP + cells and expression of TRAP and OSCAR, and loss of HMGB1 ameliorated osteoclastogenesis in OVA rats. Moreover, HMGB-1 deletion antagonized OVX-evoked downregulation of osteoblast activity markers osterix (OSX), collagen type I alpha 1(COL1A1) and distal-less homeobox 2 (DLX2) protein. Furthermore, loss of HMGB-1 attenuated fluctuation of inflammatory factors in OVX rats. Additionally, HMGB-1 deficiency inhibited OVX-evoked activation of the Toll-like receptor (TLR) 4/NF-κB signaling pathway. Moreover, reactivating the TLR4 signaling further aggravated OVX-induced osteoporosis, which was reversed by HMGB1 knockdown. CONCLUSION: HMGB-1 deletion alleviated OVX-triggered osteoporosis by suppressing osteoclastogenesis and inflammatory disorder via the inhibition of the TLR4 signaling. Therefore, HMGB-1 may be a promising therapeutic target for osteoporosis.