Testicular dysfunction and "its recovery effect" after cadmium exposure.

In recent years, with the acceleration of industrialization, the decline of male fertility caused by heavy metal pollution has attracted much attention. However, whether the inhibition of testicular function after cadmium exposure is reversible remains to be studied. In this study, we constructed rat models of cadmium exposure and dis-exposure, and collected relative samples to observe the changes of related indicators. The results showed that cadmium exposure could reduce the fertility, inhibit the hypothalamic-pituitary-testis axis and activate hypothalamic-pituitary-adrenal axis function, the testicular GR/PI3K-AKT/AMPK signal was abnormal, cell proliferation was inhibited and apoptosis was enhanced. Four weeks after the exposure was stopped, the fertility was still decreased, testicular testosterone synthesis and spermatogenesis were inhibited, cell proliferation was inhibited and apoptosis was enhanced, but all of them were reversed. After eight weeks of cadmium exposure, the above indicators were observed to return to normal. At the same time, by giving different concentrations of corticosterone to spermatogonium, we confirmed that corticosterone may regulate the proliferation and apoptosis of spermatogonium through GR/PI3K-AKT/AMPK signal. In this study, the reproductive toxicity of cadmium, a metal environmental pollutant, was analyzed in depth to provide a new theoretical and experimental basis for ensuring male reproductive health.

Self-standing bacterial cellulose-reinforced poly(3,4-ethylenedioxythiophene)/poly(4-styrenesulfonate) doped with graphene oxide composite electrodes for high-performance ionic electroactive soft actuators.

Flexible electrode films with good film-forming properties, large deformation ability, high conductivity, and strong charge and discharge capabilities are crucial for ionic electroactive polymer soft actuators. However, there are still challenges in preparing high-quality electrode films that can combine well with the intermediate polyelectrolyte to form high-performance soft actuators. Herein, we propose an advanced sandwich ionic electroactive actuator utilizing self-standing bacterial cellulose (BC) reinforced poly(3,4-ethylenedioxythiophene)/poly(4-styrenesulfonate) (PP) doped with graphene oxide (GO) conductive composite electrodes and a Nafion ion-exchange membrane via a hot-pressing method. The prepared BC-PP-GO electrodes have good film-forming properties with a Young's modulus of 1360 MPa and a high conductivity of 150 S cm-1. The hot-pressed BC-PP-GO/Nafion ionic actuator exhibited a large bending displacement of 6.2 mm (1 V, 0.1 Hz) with a long-term actuation stability up to 95% over 360 cycles without degradation. Furthermore, we introduced the actuator's potential applications including bionic grippers, flies, and fish, providing more opportunities for the development of next-generation micromanipulators and biomimetic microrobots in cm-scale space.

YTHDF1-CLOCK axis contributes to pathogenesis of allergic airway inflammation through LLPS.

N6-methyladenosine (m6A) modification has been implicated in many cell processes and diseases. YTHDF1, a translation-facilitating m6A reader, has not been previously shown to be related to allergic airway inflammation. Here, we report that YTHDF1 is highly expressed in allergic airway epithelial cells and asthmatic patients and that it influences proinflammatory responses. CLOCK, a subunit of the circadian clock pathway, is the direct target of YTHDF1. YTHDF1 augments CLOCK translation in an m6A-dependent manner. Allergens enhance the liquid-liquid phase separation (LLPS) of YTHDF1 and drive the formation of a complex comprising dimeric YTHDF1 and CLOCK mRNA, which is distributed to stress granules. Moreover, YTHDF1 strongly activates NLRP3 inflammasome production and interleukin-1ß secretion leading to airway inflammatory responses, but these phenotypes are abolished by deleting CLOCK. These findings demonstrate that YTHDF1 is an important regulator of asthmatic airway inflammation, suggesting a potential therapeutic target for allergic airway inflammation.

Heme oxygenase-1 alleviates allergic airway inflammation by suppressing NF-κB-mediated pyroptosis of bronchial epithelial cells.

Allergic asthma development and pathogenesis are influenced by airway epithelial cells in response to allergens. Heme oxygenase-1 (HO-1), an inducible enzyme responsible for the breakdown of heme, has been considered an appealing target for the treatment of chronic inflammatory diseases. Herein, we report that alleviation of allergic airway inflammation by HO-1-mediated suppression of pyroptosis in airway epithelial cells (AECs). Using house dust mite (HDM)-induced asthma models of mice, we found increased gasdermin D (GSDMD) in the airway epithelium. In vivo administration of disulfiram, a specific inhibitor of pore formation by GSDMD, decreased thymic stromal lymphopoietin (TSLP) release, T helper type 2 immune response, alleviated airway inflammation, and reduced airway hyperresponsiveness (AHR). HO-1 induction by hemin administration reversed these phenotypes. In vitro studies revealed that HO-1 restrained GSDMD-mediated pyroptosis and cytokine TSLP release in AECs by binding Nuclear Factor-Kappa B (NF-κB) p65 RHD domain and thus controlling NF-κB-dependent pyroptosis. These data provide new therapeutic indications for purposing HO-1 to counteract inflammation, which contributes to allergic inflammation control.

Efficacy and safety of agomelatine in epilepsy patients with sleep and mood disorders: An observational, retrospective cohort study.

OBJECTIVE: To evaluate the therapeutic efficacy and safety of agomelatine for treating the sleep and mood disorders in epilepsy patients. METHODS: Retrospective data were derived from 113 epilepsy patients for at least 8 weeks. All the subjects were divided into two groups, one was treated with agomelatine, the other was treated with escitalopram. Their depression and anxiety states were assessed by Hamilton Depression (HAMD) and Hamilton Anxiety (HAMA) Scales. Sleep quality was assessed by the Pittsburgh Sleep Quality Index (PSQI). RESULTS: The HAMA, HAMD and PSQI scores in both groups significantly declined after the treatments with agomelatine and escitalopram. However, the agomelatine group exhibited greater improvement in terms of HAMA and PSQI scores compared to the escitalopram group. No severe adverse events were observed in agomelatine group. SIGNIFICANCE: Agomelatine performed better in HAMA and PSQI scores compared to escitalopram, where no significant increase in seizure frequency or side effects were observed. Possibly, agomelatine presents a promising therapeutic option for treating the sleep or mood disorders in epilepsy patients.

Effects of RNA silencing during antagonism between citrus exocortis viroid and citrus bark cracking viroid in Etrog citron (Citrus medica).

Citrus exocortis viroid (CEVd) and citrus bark cracking viroid (CBCVd) are two important viroids that infect citrus plants and frequently occur as mixed infections in orchards. However, the mechanism of antagonism between the two viroids in mixed infections remains unclear. The CEVd/CBCVd-citron system and small RNA sequencing (sRNA-seq) were used to study the antagonism. When CBCVd was inoculated before CEVd, the CEVd titre was significantly reduced and the symptoms were attenuated. Viroid-derived sRNAs (vd-sRNAs) from CEVd and CBCVd were predominantly 21-nucleotide (nt) and 22-nt in length and had similar 5' base biases. Homologous sequences of the two viroids in the terminal right (TR) region are rich in vd-sRNAs, and the high frequency vd-sRNAs selected from the CBCVd TR region can be used to degrade the transcripts of CEVd in vivo directly. These results suggest that RNA silencing may play an important role in the antagonism of the two viroids, thus deepening our understanding of the molecular interaction of long noncoding RNAs in woody plants.

Cadmium exposure-induced rat testicular dysfunction and its mechanism of chronic stress.

Cadmium is a common environmental pollutant in daily life, the toxic mechanisms of chronic cadmium exposure on the testes have not been fully elucidated. This study aimed to explore the effects of cadmium exposure on male reproductive health and its mechanism. The results showed that cadmium exposure led widened interstitial spaces, abnormal seminiferous tubule morphology, and decreased Leydig cell numbers. Moreover, sperm quality was significantly reduced, along with a decrease in fertility rate. And cadmium exposure could activate the hypothalamic-pituitary-adrenal (HPA) axis, elevate blood glucocorticoid levels, subsequently increase glucocorticoid receptor (GR) expression and activation in testicular Leydig cells. Then GR act on the glucocorticoid receptor element (GRE) in the DNA methyltransferase 3 A (DNMT3A) promoter region and upregulate DNMT3A expression. Consequently, this led to an increase in DNA methylation levels in the angiotensin II receptor 2 (AT2R) promoter region, resulting in reduced AT2R expression and inhibiting testicular steroidogenesis. This study systematically elucidated that cadmium exposure could lead to testicular steroidogenesis suppression and decreased fertility through the GR/DNMT3A/AT2R signaling pathway. This research further provides theoretical and experimental evidence for confirming the threat of cadmium exposure to human reproduction, and contributes to the guidance and protection of male reproductive health.

Determinants of international Korean language promotion: A cross-country analysis.

This study investigates the determinants of the international promotion of the Korean language at the cross-country level. The analysis is based on candidate data drawn from the Test of Proficiency in Korean (TOPIK) and uses a cross-country panel data model to measure how several factors affect Korea's international promotion. To mitigate sample selection bias, we estimated the model using the Heckman two-step method. The findings show that factors such as the Hallyu (or "Korean Wave"), international business, motivation to migrate to South Korea, motivation to study in South Korea, and Korean language learning resources play essential roles in the international promotion of Korean. The development level of the sample countries influenced the importance of each factor. For example, Hallyu, often regarded as important for the international promotion of Korean, was shown to be statistically significant only in the sample of developed countries. In addition, a shortage of Korean language learning resources has been identified as a major impediment to the promotion of Koreans in developing countries. These results provide new insights that can assist in formulating policies to promote the Korean language worldwide.

A Putative TRAPα Protein of Microsporidia Nosema bombycis Exhibits Non-Canonical Alternative Polyadenylation in Transcripts.

Microsporidia are obligate intracellular eukaryotic parasites that have significantly reduced genomes and that have lost most of their introns. In the current study, we characterized a gene in microsporidia Nosema bombycis, annotated as TRAPα (HNbTRAPα). The homologous of TRAPα are a functional component of ER translocon and facilitates the initiation of protein translocation in a substrate-specific manner, which is conserved in animals but absent from most fungi. The coding sequence of HNbTRAPα consists of 2226 nucleotides, longer than the majority of homologs in microsporidia. A 3' RACE analysis indicated that there were two mRNA isoforms resulting from non-canonical alternative polyadenylation (APA), and the polyadenylate tail was synthesized after the C951 or C1167 nucleotide, respectively. Indirect immunofluorescence analysis showed two different localization characteristics of HNbTRAPα, which are mainly located around the nuclear throughout the proliferation stage and co-localized with the nuclear in mature spores. This study demonstrated that the post-transcriptional regulation mechanism exists in Microsporidia and expands the mRNA isoform repertoire.

Effects of a Synbiotic on Plasma Immune Activity Markers and Short-Chain Fatty Acids in Children and Adults with ADHD-A Randomized Controlled Trial.

Synbiotic 2000, a pre + probiotic, reduced comorbid autistic traits and emotion dysregulation in attention deficit hyperactivity disorder (ADHD) patients. Immune activity and bacteria-derived short-chain fatty acids (SCFAs) are microbiota-gut-brain axis mediators. The aim was to investigate Synbiotic 2000 effects on plasma levels of immune activity markers and SCFAs in children and adults with ADHD. ADHD patients (n = 182) completed the 9-week intervention with Synbiotic 2000 or placebo and 156 provided blood samples. Healthy adult controls (n = 57) provided baseline samples. At baseline, adults with ADHD had higher pro-inflammatory sICAM-1 and sVCAM-1 and lower SCFA levels than controls. Children with ADHD had higher baseline sICAM-1, sVCAM-1, IL-12/IL-23p40, IL-2Rα, and lower formic, acetic, and propionic acid levels than adults with ADHD. sICAM-1, sVCAM-1, and propionic acid levels were more abnormal in children on medication. Synbiotic 2000, compared to placebo, reduced IL-12/IL-23p40 and sICAM-1 and increased propionic acid levels in children on medication. SCFAs correlated negatively with sICAM-1 and sVCAM-1. Preliminary human aortic smooth-muscle-cell experiments indicated that SCFAs protected against IL-1ß-induced ICAM-1 expression. These findings suggest that treatment with Synbiotic 2000 reduces IL12/IL-23p40 and sICAM-1 and increases propionic acid levels in children with ADHD. Propionic acid, together with formic and acetic acid, may contribute to the lowering of the higher-than-normal sICAM-1 levels.

Identification and molecular characterization of a novel cytorhabdovirus from rose plants (Rosa chinensis Jacq.).

A novel negative-sense single-stranded RNA virus, tentatively named "rose-associated cytorhabdovirus" (RaCV), was identified by high-throughput sequencing. RaCV is 16,067 nucleotides in length and contains eight open reading frames (ORFs 1-8) encoding a nucleocapsid protein (N), a putative phosphoprotein (P), a putative P3 protein (P3), a putative P4 protein (P4), a putative matrix protein (M), a glycoprotein (G), a putative P7 protein (P7), and an RNA-dependent RNA polymerase (L), respectively. The coding genes are flanked by a 3' leader sequence (228 nt) and a 5' trailer sequence (251 nt) and are separated by conserved intergenic junctions (3'-AUUCUUUUUG(N)nCUN-5'). Phylogenetic analysis showed that RaCV clustered with yerba mate virus A (YmVA) within the cytorhabdovirus clade, and it exhibited low a degree of nt sequence similarity (<40% identity) to other rhabdoviruses. Amino acid sequence comparisons between the putative proteins of RaCV and the corresponding proteins of other cytorhabdoviruses showed that the sequence identity levels were far below the species demarcation cutoff of 80% for cytorhabdoviruses. These results suggest that RaCV should be classified as a new member of the genus Cytorhabdovirus.

Intra- and peritumoral radiomics for predicting early recurrence in patients with high-grade serous ovarian cancer.

PURPOSE: To explore values of intra- and peritumoral CT-based radiomics for predicting recurrence in high-grade serous ovarian cancer (HGSOC) patients. METHODS: This study enrolled 110 HGSOC patients from our hospital between Aug 2017 and Apr 2021. All patients underwent contrast-enhanced CT scans before treatment. The least absolute shrinkage and selection operator (LASSO) regression was used to select radiomics features from intra- and peritumoral areas. Radiomics signatures were built based on selected features from Intra-RS, Peri-RS, and in Com-RS. A nomogram was constructed by combining radiomics signatures and clinical parameters with predictive potential. Receiver operating characteristics (ROC), calibration, and decision curve analyses (DCA) curves were used to evaluate performance of the nomogram. RESULTS: The intra- and peritumoral combined Com-RS showed effective ability in predicting recurrent HGSOC in the training (AUCs, Intra-RS vs. Peri-RS vs. Com-RS, 0.861 vs. 0.836 vs. 899) and validation (AUCs, Intra-RS vs. Peri-RS vs. Com-RS, 0.788 vs. 0.762 vs. 815) cohort. The Federation of International of FIGO stage, menstruation, and location were found to be strongly associated with tumor recurrence. The nomogram has the best predictive ability in the training (AUCs, Com-RS vs. clinical model vs. nomogram, 0.899 vs. 0.648 vs. 0.901) and validation (AUCs, Com-RS vs. clinical model vs. nomogram, 0.815 vs. 0.666 vs. 0.818) cohort. CONCLUSION: Our findings suggested values of intra- and peritumoral-based radiomics for predicting recurrent HGSOC. The constructed nomogram may be of importance in clinical application.

Attenuation of experimental osteoarthritis with human adipose-derived mesenchymal stem cell therapy: inhibition of the pyroptosis in chondrocytes.

AIM: To explore the role and mechanism of human adipose-derived mesenchymal stem cells (hAD-MSCs) in the treatment of osteoarthritis (OA). METHODS: OA hulth model of Sprague Dawley (SD) rats and 20 ng/ml TNF-α treated chondrocytes were used as models of OA in vivo and in vitro, respectively. hAD-MSCs were administrated in the articular cavity by injection in vivo and co-cultured with chondrocytes using transwell in vitro. Haematoxylin and eosin staining and Safranin-O/Fast green staining were performed to detect tissue destruction and histopathology. Scanning electron microscopy and transmission electron microscopy were used to observe the ultrastructure of chondrocytes. The pyroptosis signaling pathway-related proteins were detected by immunohistochemistry, immunofluorescence, qRT-PCR and Western blot. And small interference technology was used to study the mechanism in depth. RESULTS: hAD-MSCs could delay the development of rat OA, improve the pathological changes of joints, inhibit the expression of NLRP3, Caspase1, GSDMD and TNFR1. In vitro, the expression of pyroptosis signal proteins in chondrocytes was significantly elevated when stimulated with TNF-α, the level of inflammatory factors such as IL-1ß, IL-18 was increased, and the cell morphology was significantly destroyed. While co-cultured with hAD-MSCs, these syndromes were reversed. Knockout of TNFR1 also returned the upregulation of pyroptosis signals which caused by TNF-α. CONCLUSION: These results demonstrated that hAD-MSCs could inhibit pyroptosis signaling pathway of chondrocytes induced by TNF-α, which have raised our understanding of the role of hAD-MSCs as promising therapy for the management of OA.

Radiomics for Detection of the EGFR Mutation in Liver Metastatic NSCLC.

RATIONALE AND OBJECTIVES: The research aims to investigate whether MRI radiomics on hepatic metastasis from primary nonsmall cell lung cancer (NSCLC) can be used to differentiate patients with epidermal growth factor receptor (EGFR) mutations from those with EGFR wild-type, and develop a prediction model based on combination of primary tumor and the metastasis. MATERIALS AND METHODS: A total of 130 patients were enrolled between Aug. 2017 and Dec. 2021, all pathologically confirmed harboring hepatic metastasis from primary NSCLC. The pyradiomics was used to extract radiomics features from intra- and peritumoral areas of both primary tumor and metastasis. The least absolute shrinkage and selection operator (LASSO) regression was applied to identify most predictive features and to develop radiomics signatures (RSs) for prediction of the EGFR mutation status. The receiver operating characteristic (ROC) curve analysis was performed to assess the prediction capability of the developed RSs. RESULTS: A RS-Primary and a RS-Metastasis were derived from the primary tumor and metastasis, respectively. The RS-Combine by combination of the primary tumor and metastasis achieved the highest prediction performance in the training (AUCs, RS-Primary vs. RS-Metastasis vs. RS-Combine, 0.826 vs. 0.821 vs. 0.908) and testing (AUCs, RS-Primary vs. RS-Metastasis vs. RS-Combine, 0.760 vs. 0.791 vs. 0.884) set. The smoking status showed significant difference between EGFR mutant and wild-type groups (p < 0.05) in the training set. CONCLUSION: The study indicates that hepatic metastasis-based radiomics can be used to detect the EGFR mutation. The developed multiorgan combined radiomics signature may be helpful to guide individual treatment strategies for patients with metastatic NSCLC.

Radiomics signatures for predicting the Ki-67 level and HER-2 status based on bone metastasis from primary breast cancer.

This study explores the potential of radiomics to predict the proliferation marker protein Ki-67 levels and human epidermal growth factor receptor 2 (HER-2) status based on MRI images of patients with spinal metastasis from primary breast cancer. A total of 110 patients with pathologically confirmed spinal metastases from primary breast cancer were enrolled between Dec. 2017 and Dec. 2021. All patients underwent T1-weighted contrast-enhanced MRI scans. The PyRadiomics package was used to extract features from the MRI images based on the intraclass correlation coefficient and least absolute shrinkage and selection operator. The most predictive features were used to develop the radiomics signature. The Chi-Square test, Fisher's exact test, Student's t-test, and Mann-Whitney U test were used to evaluate the clinical and pathological characteristics between the high- and low-level Ki-67 groups and the HER-2 positive/negative groups. The radiomics models were compared using receiver operating characteristic curve analysis. The area under the receiver operating characteristic curve (AUC), sensitivity (SEN), and specificity (SPE) were generated as comparison metrics. From the spinal MRI scans, five and two features were identified as the most predictive for the Ki-67 level and HER-2 status, respectively. The developed radiomics signatures generated good prediction performance for the Ki-67 level in the training (AUC = 0.812, 95% CI: 0.710-0.914, SEN = 0.667, SPE = 0.846) and validation (AUC = 0.799, 95% CI: 0.652-0.947, SEN = 0.722, SPE = 0.833) cohorts. Good prediction performance for the HER-2 status was also achieved in the training (AUC = 0.796, 95% CI: 0.686-0.906, SEN = 0.720, SPE = 0.776) and validation (AUC = 0.705, 95% CI: 0.506-0.904, SEN = 0.733, SPE = 0.762) cohorts. The results of this study provide a better understanding of the potential clinical implications of spinal MRI-based radiomics on the prediction of Ki-67 levels and HER-2 status in breast cancer.

LDHA: The Obstacle to T cell responses against tumor.

Immunotherapy has become a successful therapeutic strategy in certain solid tumors and hematological malignancies. However, this efficacy of immunotherapy is impeded by limited success rates. Cellular metabolic reprogramming determines the functionality and viability in both cancer cells and immune cells. Extensive research has unraveled that the limited success of immunotherapy is related to immune evasive metabolic reprogramming in tumor cells and immune cells. As an enzyme that catalyzes the final step of glycolysis, lactate dehydrogenase A (LDHA) has become a major focus of research. Here, we have addressed the structure, localization, and biological features of LDHA. Furthermore, we have discussed the various aspects of epigenetic regulation of LDHA expression, such as histone modification, DNA methylation, N6-methyladenosine (m6A) RNA methylation, and transcriptional control by noncoding RNA. With a focus on the extrinsic (tumor cells) and intrinsic (T cells) functions of LDHA in T-cell responses against tumors, in this article, we have reviewed the current status of LDHA inhibitors and their combination with T cell-mediated immunotherapies and postulated different strategies for future therapeutic regimens.

Down-Regulation of Lipid Metabolism in the Hepatopancreas of Shrimp Litopenaeus vannamei upon Light and Heavy Infection of Enterocytozoon hepatopenaei: A Comparative Proteomic Study.

Enterocytozoon hepatopenaei (EHP) is the pathogen of hepatopancreatic microsporidiosis (HPM) in shrimp. The diseased shrimp Litopenaeus vannamei exhibits a slow growth syndrome, which causes severe economic losses. Herein, 4D label-free quantitative proteomics was employed to analyze the hepatopancreas of L. vannamei with a light (EHPptp2 < 103 copies/50 ng hpDNA, L group) and heavy (EHPptp2 > 104 copies/50 ng hpDNA, H group) load of EHP to better understand the pathogenesis of HPM. Exactly 786 (L group) and 1056 (H group) differentially expressed proteins (DEPs) versus the EHP-free (C group) control were mainly clustered to lipid metabolism, amino acid metabolism, and energy production processing. Compared with the L group, the H group exhibited down-regulation significantly in lipid metabolism, especially in the elongation and degradation of fatty acid, biosynthesis of unsaturated fatty acid, metabolism of α-linolenic acid, sphingolipid, and glycerolipid, as well as juvenile hormone (JH) degradation. Expression pattern analysis showed that the degree of infection was positively correlated with metabolic change. About 479 EHP proteins were detected in infected shrimps, including 95 predicted transporters. These findings suggest that EHP infection induced the consumption of storage lipids and the entire down-regulation of lipid metabolism and the coupling energy production, in addition to the hormone metabolism disorder. These were ultimately responsible for the stunted growth.

Measurement of Cable Force through a Fiber Bragg Grating-Type Thin Rod Vibration Sensor and Its Application.

The key to evaluating the health status of cable-stayed bridges lies in the accuracy of cable force measurement. When measuring the cable force using the conventional frequency method, the clearance between the bracing cable and the protective tube is typically disregarded. Moreover, due to their large size, existing vibration sensors are difficult to install into protective tubes for steel strand-type bracing cables to measure the cable force. To address the above difficulties, a type of thin rod vibration sensor only 5 mm in diameter was designed based on the high sensitivity of Fiber Bragg grating (FBG), and high-throughput data processing software for engineering calculation (EC) was self-developed. Then, the recognition principle of the thin rod vibration sensor was theoretically analyzed and a step-by-step tension test was carried out. The results demonstrated that the relative error of the cable force measured by the thin rod vibration sensor within 12.865 Hz was less than 5% and the sensitivity reached 28.7 pm/Hz, indicating its high measurement precision. Upon subsequent application of the thin rod vibration sensor to a monitoring test in the field, the relative error of the fundamental frequency between artificial and natural excitations was less than 4%. In addition, the error relative to both the theoretical frequency and the third-party sampling frequency was less than 5%, further verifying the accuracy and applicability for monitoring the cable force of bridges under natural excitation. Compared with the traditional cantilever FBG sensor, the improved sensor with supporting data processing software has the advantages of small cross-section, high reliability, and good sensitivity. The research results can provide a reference for the subsequent accurate measurement of cable force and the development of a supporting sensor data processing system.

Cytokines/chemokines and soluble immune checkpoint molecules in anti-GABAB receptor encephalitis.

BACKGROUND: Anti-gamma-aminobutyric-acid B receptor (anti-GABABR) encephalitis is a rare form of autoimmune limbic encephalitis (ALE) that is closely associated with tumor comorbidity. The purpose of this study is to identify the expressive pattern of cytokines/ chemokines and soluble immune checkpoint molecules (sICMs) in anti-GABABR encephalitis in order to evaluate the clinical condition and provide new treatment options. METHODS: A total of 40 cytokines/chemokines and 10 sICMs in the serum of 10 patients with anti-GABABR encephalitis and eight controls were measured. The differentially expressed cytokines/chemokines and sICMs were selected to explore the correlations with disease prognosis, CSF routine and antibody titers. RESULTS: Eight cytokines/chemokines were found to be more abundant in patients than in healthy donors (HDs), while 14 were found to be less abundant in patients. In terms of sICMs, patients' serum contained higher level of soluble ICOS and ICOSL but lower level of soluble CD86. Unfavorable prognosis was associated with high serum level of PDGFB, IL-17A, and soluble ICOSL but not with low levels of IL-4. Increased levels of IL-17A, CCL15, and soluble ICOS were found frequently in the patients with CSF-exclusive OCBs, while soluble ICOSL and CCL24 expression was lower in these patients. High levels of IL-1 F2 and TCA-3 were correlated with the presence of tumors in patients. CONCLUSION: The majority of patients with anti- GABABR encephalitis had an unfavorable prognosis in one year of follow-up. Serum PDGFB, IL-17A, IL-4 and soluble ICOSL level were associated with the poor clinical outcomes in one-year follow up.