Establishment and characterization of NCC-SS6-C1: a novel patient-derived cell line of synovial sarcoma.

Synovial sarcoma (SS) is identified as a sarcoma with monomorphic blue spindle cells that display variable epithelial differentiation and is characterized by the SS18::SSX fusion gene. SS accounts for approximately 5-10% of all soft tissue sarcomas, making it a relatively common type within this group of tumors. Since SS is generally sensitive to chemotherapy, the standard treatment for SS includes extensive surgical resection, complemented by neoadjuvant chemotherapy with several approved anticancer drugs. However, in advanced and metastatic cases, the efficacy of these drugs is limited, resulting in poor prognoses. This underscores the need for innovative therapeutic strategies. Patient-derived cancer cell lines are essential tools for basic and preclinical research, yet only four SS cell lines are publicly available. To facilitate the studies of SS, we have developed a novel SS cell line, named NCC-SS6-C1, derived from surgically excised tumor tissue of an SS patient. NCC-SS6-C1 cells preserve the SS18::SSX1 fusion gene, consistent with the genetic characteristics of the original tumor. The cells exhibit continuous proliferation, invasiveness, and the ability to form spheroids. Additionally, we confirmed that this cell line was useful for evaluating the efficacy of anticancer drugs. Our results suggest that NCC-SS6-C1 is a useful tool for basic and pre-clinical studies of SS.

13C CSA Tensors and Orientational Order of Model and Dimer Mesogens Comprising of Phenyl Benzoate.

A Model mesogen and its symmetrical Dimer made up of phenyl benzoate core unit are investigated by 13C NMR spectroscopy. The existence of layer order in smectic A and smectic C phases of Dimer mesogen is established by powder X-ray diffraction. The chemical shift anisotropy (CSA) tensors of Model mesogen are determined by 2D separation of undistorted powder patterns by effortless recoupling (SUPER) experiment and are utilized for calculating the order parameters employing the alignment-induced chemical shifts (AIS). Additionally, 2D separated local field (SLF) NMR is availed for extracting 13C-1H dipolar couplings for both mesogens and used for computing the order parameters. A good agreement in the order parameters calculated from 13C-1H dipolar couplings and AIS is observed. Accordingly, the main order parameter (Szz) for the phenyl rings of the Model mesogen is found to be in the range 0.54 - 0.82, and for the Dimer mesogen, the values span 0.64 - 0.82 across mesophases. Since the phenyl benzoate core unit is frequently employed structural moiety for constructing the main chain as well as side chain liquid crystalline polymers and liquid crystalline elastomers, the CSA tensors reported here will be of immense utility for the structural characterization of these materials.

Proton-Coupled Electron Transfer on Cu2O/Ti3C2Tx MXene for Propane (C3H8) Synthesis from Electrochemical CO2 Reduction.

Electrochemical CO2 reduction reaction (CO2RR) to produce value-added multi-carbon chemicals has been an appealing approach to achieving environmentally friendly carbon neutrality in recent years. Despite extensive research focusing on the use of CO2 to produce high-value chemicals like high-energy-density hydrocarbons, there have been few reports on the production of propane (C3H8), which requires carbon chain elongation and protonation. A rationally designed 0D/2D hybrid Cu2O anchored-Ti3C2Tx MXene catalyst (Cu2O/MXene) is demonstrated with efficient CO2RR activity in an aqueous electrolyte to produce C3H8. As a result, a significantly high Faradaic efficiency (FE) of 3.3% is achieved for the synthesis of C3H8 via the CO2RR with Cu2O/MXene, which is ≈26 times higher than that of Cu/MXene prepared by the same hydrothermal process without NH4OH solution. Based on in-situ attenuated total reflection-Fourier transform infrared spectroscopy (ATR-FTIR) and density functional theory (DFT) calculations, it is proposed that the significant electrocatalytic conversion originated from the synergistic behavior of the Cu2O nanoparticles, which bound the *C2 intermediates, and the MXene that bound the *CO coupling to the C3 intermediate. The results disclose that the rationally designed MXene-based hybrid catalyst facilitates multi-carbon coupling as well as protonation, thereby manipulating the CO2RR pathway.

[Correlation of anti-C1q antibodies with active systemic lupus erythematosus and lupus nephritis in children]. / 抗C1qæŠ—ä½“ä¸Žå„¿ç«¥æ´»åŠ¨æ€§ç³»ç»Ÿæ€§çº¢æ–‘ç‹¼ç–®å’Œæ´»åŠ¨æ€§ç‹¼ç–®æ€§è‚¾ç‚Žçš„ç›¸å ³æ€§åˆ†æž.

OBJECTIVES: To study the correlation of anti-C1q antibodies with active systemic lupus erythematosus (SLE) and lupus nephritis (LN) in children, as well as their diagnostic value for active SLE and LN. METHODS: A retrospective selection of 90 hospitalized children with SLE at the Children's Medical Center of Second Xiangya Hospital, Central South University from January 2016 to March 2019 as the SLE group, all of whom were tested for anti-C1q antibodies. A control group was formed by collecting 70 hospitalized children with other autoimmune diseases (OAD) during the same period. The differences in anti-C1q antibody levels were compared between two groups.The correlation of anti-C1q antibodies with various indicators of SLE and LN was analyzed, and the diagnostic value of anti-C1q in SLE and LN was evaluated. RESULTS: The serum levels of anti-C1q antibodies in the SLE group were higher than those in the OAD group (P<0.05). The SLE disease activity index score was positively correlated with anti-C1q antibodies (rs=0.371, P<0.001) and positively correlated with anti-double-stranded DNA antibodies (rs=0.370, P<0.001). The sensitivity and specificity of anti-C1q antibodies for diagnosing active SLE were 89.90% and 53.90%, respectively, with an area under the curve of 0.720 (P<0.05) and a critical value of 5.45 U/mL. The sensitivity and specificity of anti-C1q antibody levels for diagnosing active LN were 58.50% and 85.00%, respectively, with an area under the curve of 0.675 (P<0.05) and a critical value of 22.05 U/mL. CONCLUSIONS: Anti-C1q antibodies can serve as non-invasive biomarkers for evaluating the activity of SLE or predicting the activity of LN in children.

A Natural Chalcone Cardamonin Inhibited Transformation of Aryl Hydrocarbon Receptor Through Binding to the Receptor Competitively.

SCOPE: Chalcones are widely present in most plants and have various health beneficial functions. This study investigates the suppressive effect of 13 natural and synthetic chalcones on transformation of aryl hydrocarbon receptor (AhR) induced by 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and 3-methylcholanthrene (3-MC) in a cell-free system, Hepa-1c1c7 cells, and liver of ICR mice. METHODS AND RESULTS: In the cell-free system, cardamonin dose-dependently inhibits AhR transformation. Chalcones with substitution on 2' and/or 6' position is important for the suppressive effect, while the substitution on 4' position is negatively for the effect. Moreover, cardamonin and 2'-hydroxychalcone competitively inhibit the binding of [3H]-3-MC to the AhR. In Hepa-1c1c7 cells, cardamonin inhibits AhR transformation and expression of cytochrome P4501A1 (CYP1A1) in a dose-dependent manner through suppressing TCDD-induced phosphorylation of both AhR and AhR nuclear translocator, heterodimerization of them, and nuclear translocation of AhR. In the liver of mice, oral administered cardamonin also inhibits 3-MC-induced AhR translocation and expression of CYP1A1. CONCLUSION: Among used chalcones, a natural chalcone cardamonin competitively binds to AhR and suppresses its transformation. Thus, cardamonin is an effective food factor for suppression of the dioxin-caused biochemical alterations and toxicities.

Toward structure and metabolism of glycogen C1-C6 in humans at 7 T by localized 13C MRS using low-power bilevel broadband 1H decoupling.

This work aims to develop and implement a pulse-acquire sequence for three-dimensional (3D) single-voxel localized 13C MRS in humans at 7 T, in conjunction with bilevel broadband 1H decoupling, and to test its feasibility in vitro and in vivo in human calf muscle with emphasis on the detection of glycogen C1-C6. A localization scheme suitable for measuring fast-relaxing 13C signals in humans at 7 T was developed and implemented using the outer volume suppression (OVS) and one-dimensional image selected in vivo spectroscopy (ISIS-1D) schemes, similar to that which was previously reported in humans at 4 T. The 3D 13C localization scheme was followed by uniform 13C adiabatic excitation, all complemented with an option for bilevel broadband 1H decoupling to improve both 13C sensitivity and spectral resolution at 7 T. The performance of the pulse-acquire sequence was investigated in vitro on phantoms and in vivo in the human calf muscle of three healthy volunteers, while measuring glycogen C1-C6. In addition, T1 and T2 of glycogen C1-C6 were measured in vitro at 7 T, as well as T1 of glycogen C1 in vivo. The glycerol C2 and C1,3 lipid resonances were efficiently suppressed in vitro at 7 T using the OVS and ISIS-1D schemes, allowing distinct detection of glycogen C2-C6. While some glycerol remained in calf muscle in vivo, the intense lipid at 130 ppm was efficiently suppressed. The 13C sensitivity and spectral resolution of glycogen C1-C6 in vitro and glycogen C1 in vivo were improved at 7 T using bilevel broadband 1H decoupling. The T1 and T2 of glycogen C1-C6 in vitro at 7 T were consistent compared with those at 8.5 T, while the T1 of glycogen C1 in vivo at 7 T resulted similar to that in vitro. Localized 13C MRS is feasible in human calf muscle in vivo at 7 T, and this will allow further extension of this method for 13C MRS measurements such as in the brain.

A Mutation Losing an RBP-Binding Site in the LncRNA NORSF Transcript Influences Granulosa Cell Apoptosis and Sow Fertility.

Sow fertility is an economically important quantitative trait. Hundreds of quantitative trait loci (QTLs) containing tens of thousands of potential candidate genes are excavated. However, among these genes, non-coding RNAs including long non-coding RNAs (lncRNAs) are often overlooked. Here, it is reported that NORSF is a novel causal lncRNA for sow fertility traits in QTLs. QTLs are characterized for sow fertility traits at the genome-wide level and identified 4,630 potential candidate lncRNAs, with 13 differentially expressed during sow follicular atresia. NORSF, a lncRNA that involved in sow granulosa cell (sGC) function, is identified as a candidate gene for sow fertility traits as a G to A transversion at 128 nt in its transcript is shown to be markedly associated with sow fertility traits. Mechanistically, after forming the RNA:dsDNA triplexes with the promoter of Caspase8, NORSF transcript with allele G binds to an RNA-binding protein (RBP) NR2C1 and recruits it to the promoter of Caspase8, to induce Caspase8 transcription in sGCs. Functionally, this leads to a loss of inducing effect of NORSF on sGC apoptosis by inactivating the death receptor-mediated apoptotic pathway. This study identified a novel causal lncRNA that can be used for the genetic improvement of sow fertility traits.

Functional plasticity of HCO3- uptake and CO2 fixation in Cupriavidus necator H16.

Despite its prominence, the ability to engineer Cupriavidus necator H16 for inorganic carbon uptake and fixation is underexplored. We tested the roles of endogenous and heterologous genes on C. necator inorganic carbon metabolism. Deletion of ß-carbonic anhydrase can had the most deleterious effect on C. necator autotrophic growth. Replacement of this native uptake system with several classes of dissolved inorganic carbon (DIC) transporters from Cyanobacteria and chemolithoautotrophic bacteria recovered autotrophic growth and supported higher cell densities compared to wild-type (WT) C. necator in batch culture. Strains expressing Halothiobacillus neopolitanus DAB2 (hnDAB2) and diverse rubisco homologs grew in CO2 similarly to the wild-type strain. Our experiments suggest that the primary role of carbonic anhydrase during autotrophic growth is to support anaplerotic metabolism, and an array of DIC transporters can complement this function. This work demonstrates flexibility in HCO3- uptake and CO2 fixation in C. necator, providing new pathways for CO2-based biomanufacturing.

Low serum CTRP3 is related to more severe distal symmetric polyneuropathy in type 2 diabetes patients.

BACKGROUND: Distal symmetric polyneuropathy (DSPN) is one of the most common chronic complications in patients with type 2 diabetes mellitus (T2DM). Our previous study found that serum C1q tumor necrosis factor-related protein 3 (CTRP3) levels were decreased in type 2 diabetic patients. Thus, this study was designed to reveal the relationship between low serum CTRP3 and the prevalence and severity of DSPN. METHODS: A total of 178 cases of patients with T2DM were enrolled in the study. The subjects were divided into the DSPN group (n = 89) and the non-DSPN group (n = 89). Both anthropometric parameters and neurologic symptoms were recorded. Furthermore, neurologic signs, the neuropathy symptom score (NSS), and the neuropathy disability score (NDS) were assessed. Biochemical indexes, fasting insulin, and C peptide were measured. Serum CTRP3 concentrations were assayed using the ELISA method. RESULTS: Serum CTRP3 levels decreased significantly in the DSPN group compared with the non-DSPN group (P < 0.05). CTRP3 was negatively associated with the number of positive signs, NSS score, and NDS score in patients with DSPN (all P < 0.05). Interestingly, the higher the NSS score or NDS score, the lower were the levels of serum CTRP3 (all P < 0.05). Moreover, patients with lower CTRP3 levels (< 7.58ng/ml) had a higher rate of neurologic signs (all P < 0.05). Binary logistic regression analysis showed that CTRP3 independently predicted the occurrence of DSPN (ß = -0.316, P < 0.001). ROC curve analysis revealed that the best cut-off value of CTRP3 for the prediction of DSPN was 7.55ng/ml (sensitivity 78.7%, specificity 79.8%), the area under the curve (AUC) was 0.763 (95% CI 0.689-0.838, P < 0.001). CONCLUSION: Low serum CTRP3 could be a predictor for the occurrence and progression of DSPN in Chinese patients with T2DM.

Downregulation of C1R promotes hepatocellular carcinoma development by activating HIF-1α-regulated glycolysis.

C1R has been identified to have a distinct function in cutaneous squamous cell carcinoma that goes beyond its role in the complement system. However, it is currently unknown whether C1R is involved in the progression of hepatocellular carcinoma (HCC). HCC tissues were used to examine C1R expression in relation to clinical and pathological factors. Malignant characteristics of HCC cells were assessed through in vitro and in vivo experiments. The mechanism underlying the role of C1R in HCC was explored through RNA-seq, methylation-specific PCR, immuno-precipitation, and dual-luciferase reporter assays. This study found that the expression of C1R decreased as the malignancy of HCC increased and was associated with poor prognosis. C1R promoter was highly methylated through DNMT1 and DNMT3a, resulting in a decrease in C1R expression. Downregulation of C1R expression resulted in heightened malignant characteristics of HCC cells through the activation of HIF-1α-mediated glycolysis. Additionally, decreased C1R expression was found to promote xenograft tumor formation. We found that C-reactive protein (CRP) binds to C1R, and the free CRP activates the NF-κB signaling pathway, which in turn boosts the expression of HIF-1α. This increase in HIF-1α leads to higher glycolysis levels, ultimately promoting aggressive behavior in HCC. Methylation of the C1R promoter region results in the downregulation of C1R expression in HCC. C1R inhibits aggressive behavior in HCC in vitro and in vivo by inhibiting HIF-1α-regulated glycolysis. These findings indicate that C1R acts as a tumor suppressor gene during HCC progression, opening up new possibilities for innovative therapeutic approaches.

Pediatric Bilateral Hypoplastic Kidney Complicated With C1q Nephropathy: A Case Report.

Progressive kidney dysfunction is often observed in children with bilateral hypoplastic kidneys. While glomerulopathy can exacerbate hypoplastic kidney progression, only IgA nephropathy and post-streptococcal acute glomerulonephritis have been noted in such cases. Herein, we present a case of a four-year-old female patient with bilateral hypoplastic kidney, kidney dysfunction, and significant proteinuria (urinary protein/creatinine ratio > 1 g/gCr), prompting referral owing to persistent hematuria since two years of age. Enalapril was initiated; however, urinary findings exhibited no improvement despite stable symptoms and kidney function. Subsequently, a kidney biopsy was performed at six years of age, and C1q nephropathy was diagnosed. Given the presence of only mild mesangial proliferation, steroids were not administered; enalapril treatment was continued. By seven years of age, the patient's hematuria had resolved, and proteinuria levels had decreased. On the latest follow-up at 12 years of age, kidney function was preserved with only mild proteinuria. This case report highlights the favorable prognosis of asymptomatic C1q nephropathy characterized by mild mesangial proliferation, even in patients with hypoplastic kidneys, renal dysfunction, and significant proteinuria. It emphasizes the significance of timely pathological evaluation for guiding appropriate interventions in such patients.

Influence of fecal fermentation on the anthelmintic activity of proanthocyanidins and ellagitannins against human intestinal nematodes and Caenorhabditis elegans.

Some tannin-rich plants such as Combretum mucronatum and Phyllanthus urinaria are widely used in Africa for the control of parasitic nematodes in both humans and livestock. Tannins have been recognized as an alternative source of anthelmintic therapies, and hence, recent studies have focused on both the hydrolyzable and condensed tannins. These groups of compounds, however, have poor oral bioavailability and are metabolized by gut microbiota into lower molecular weight compounds. The role of these metabolites in the anthelmintic activities of tannins has not been explored yet. This study investigated the effects of fecal metabolism on the anthelmintic potential of procyanidin C1 (PC1) and geraniin and the tannin-enriched extracts of C. mucronatum (CML) and P. urinaria (PUH), which contain these compounds, respectively. Metabolites were formed by anaerobic fermentation of the test compounds and extracts in a fresh human fecal suspension for 0 h, 4 h, and 24 h. Lyophilized samples were tested in vitro against hookworm larvae and whipworm (Trichuris trichiura) larvae obtained from naturally infected human populations in Pru West District, Bono East Region, Ghana, and against the wildtype strain of Caenorhabditis elegans (L4). Both extracts and compounds in the undegraded state exhibited concentration-dependent inhibition of the three nematodes. Their activity, however, significantly decreased upon fecal metabolism. Without fermentation, the proanthocyanidin-rich CML extract was lethal against hookworm L3 (LC50 = 343.5 µg/mL, 95% confidence interval (CI) = 267.5-445.4), T. trichiura L1 (LC50 = 230.1 µg/mL, CI = 198.9-271.2), and C. elegans (LC50 = 1468.1 µg/mL, CI = 990.3-1946.5). PUH, from which the ellagitannin geraniin was isolated, exhibited anthelmintic effects in the unfermented form with LC50 of 300.8 µg/mL (CI = 245.1-374.8) against hookworm L3 and LC50 of 331.6 µg/mL (CI = 290.3-382.5) against T. trichiura L1, but it showed no significant activity against C. elegans L4 larvae at the tested concentrations. Similarly, both compounds, procyanidin C1 and geraniin, lost their activity when metabolized in fecal matter. The activity of geraniin at a concentration of 170 µg/mL against C. elegans significantly declined from 30.4% ± 1.8% to 14.5% ± 1.5% when metabolized for 4 h, whereas that of PC1 decreased from 32.4% ± 2.3% to 8.9% ± 0.9% with similar treatment. There was no significant difference between the anthelmintic actions of metabolites from the structurally different tannin groups. The outcome of this study revealed that the intact bulky structure of tannins (hydrolyzable or condensed) may be required for their anthelmintic action. The fermented products from the gut may not directly contribute toward the inhibition of the larvae of soil-transmitted helminths.

Feasibility and Safety of Lateral and Posterolateral Percutaneous Vertebroplasty of Osteolytic C1-C2 Lesions under Computed Tomography Guidance and Local Anesthesia.

OBJECTIVE: To evaluate the safety and effectiveness of the lateral or posterolateral percutaneous vertebroplasty (PVP) of osteolytic C1-C2 lesions performed under computed tomography (CT) guidance and local anesthesia. MATERIALS AND METHODS: Retrospective study of 16 consecutive patients (11 females and 5 males, aged from 24 to 86 years, median 65.5 years) who underwent 17 lateral or posterolateral PVP. Pain status was assessed using a visual analog scale (VAS). Patients were evaluated preoperatively as baseline and at 24 hours, 1, 6, 12 months postoperatively, or until the patient died or was lost to follow-up. The Oswestry Disability Index (ODI) was used to evaluate the patients' functional disability preoperatively. The adverse events were recorded using the SIR classification. RESULTS: The technical success was 100% (17/17) for a median SINS score about 13.5 (IQR [6.75, 20.25]). Mean clinical follow up was 10.1 months (range, 6-36 months; median 19.5 months, IQR [4, 35]). Mean VAS score decreased significantly from 7.5 ± 2.1 preoperatively to 1.6 ± 1.5 24 hours postoperatively, and 1.0 ± 1.1, 1.5 ± 1, and 0.5 ± 1.5 at 1, 6, 12 months respectively (all p<.001). No severe adverse events were observed but 3 cases of asymptomatic cement leakage (SIR grade 1) (17.6% (3/17)). CONCLUSIONS: Lateral and posterolateral PVP performed under CT guidance and local anesthesia is safe and effective to treat symptomatic osteolytic C1-C2 lesions.

Causal relationship between complement C1QB and colorectal cancer: a drug target Mendelian randomization study.

Background: Colorectal cancer is influenced by several factors such as unhealthy habits and genetic factors. C1QB has been linked to a number of malignancies. However, uncertainty surrounds the connection between C1QB and CRC. Therefore, this study aimed to explore a bidirectional causal relationship of C1QB as a drug target in CRC through Mendelian randomization (MR) analysis. Methods: The GWASs for C1QB and CRC were obtained from the Integrative Epidemiology Unit Open GWAS database. There were five strategies to investigate MR. Sensitivity analysis was carried out via tests for heterogeneity, horizontal pleiotropy and leave-one-out effects to evaluate the dependability of the MR analysis results. Furthermore, colocalization analysis of C1QB and CRC, protein-protein interaction network and drug prediction according to exposure factors as well as phenotype scanning were performed. Results: The results of forward MR analysis demonstrated that C1QB was a risk factor for CRC (OR = 1.104, p = 0.033). However, we did not find a causal relationship between CRC and C1QB (reverse MR). Rs294180 and rs291985 corresponded to the same linkage interval and had the potential to influence C1QB and CRC, respectively. The PPI results demonstrated that C1QB interacted with 10 genes (C1QA, C1QC, C1R, C1S, C2, C4A, C4B, CALR, SERPING1, and VSIG4). Additionally, 21 medications were predicted to match C1QB. Molecular docking data, including for benzo(a)pyrene, 1-naphthylisothiocyanate, calcitriol and medroxyprogesterone acetate, revealed excellent binding for drugs and proteins. Moreover, we identified 29 diseases that were associated with C1QB and related medicines via disease prediction and intersection methods. As a therapeutic target for CRC, phenotypic scanning revealed that C1QB does not significantly affect weight loss, liver cirrhosis, or nonalcoholic fatty liver disease, but might have protective impacts on ovarian cancer and melanoma. Conclusion: The results highlight a causal relationship between C1QB and CRC and imply an oncogenic role for C1QB in CRC, as potential drug targets. Drugs designed to target C1QB have a greater chance of success in clinical trials and are expected to help prioritize CRC drug development and reduce drug development costs. That provided a theoretical foundation and reference for research on CRC and C1QB in MR.

Jung, the Rebirth Motif and Psychedelics I: Documenting Jung's Contact with the British Pioneers.

C. G. Jung wrote very little about psychedelic drugs and he took a sceptical view of them. However, he was sufficiently impressed by Aldous Huxley's 1954 account of taking mescaline, The Doors of Perception, to invite Huxley to visit him in Switzerland. Huxley declined Jung's invitation but Huxley's collaborator Humphry Osmond met Jung instead. This paper documents Jung's contact with the British pioneers of psychedelics research and presents the scant material illuminating his views about these drugs. It also determines the efforts of British psychiatrist Ronald Sandison, who was the first to develop an "explicitly Jungian approach" to psychedelic-assisted psychotherapy (Hill, 2013), and it highlights a connection between Sandison's initiative and the Society of Analytical Psychology (SAP) through the involvement of two SAP members: Margot Cutner, Sandison's colleague, and Michael Fordham, who supervised a trainee working with one of Sandison's former patients. Despite Jung's objections to the use of psychedelics, Sandison and Cutner developed ground-breaking protocols during the 1950s and they were among the first to document the phenomenon of "spiritual rebirth symbolized in the birth experience known to many LSD therapists" (Sandison, 2001). In two companion papers, I consider Jung's treatment of the rebirth motif in his commentary on The Tibetan Book of the Dead, which later became a central text in the psychedelic movement, and I chart the evolution in psychedelics research from an association with schizophrenia during the 1950s to the mystical paradigms of the 1960s and beyond.

C.G. Jung a très peu écrit sur les drogues psychédéliques et il avait à leur égard une attitude sceptique. Cependant il fut suffisamment impressionné par le récit d'Aldous Huxley de son expérience avec la mescaline en 1954, Les Portes de la Perception, pour inviter Huxley à lui rendre visite en Suisse. Huxley déclina l'invitation de Jung mais son collaborateur Humphry Osmond rencontra Jung à sa place. Cet article rend compte des contacts de Jung avec les recherches des pionniers britanniques en matière de drogues psychédéliques. Il présente aussi le peu de matériel qui illustre ses opinions concernant ces drogues. L'article explore les efforts du psychiatre britannique Ronald Sandison ­ qui fut le premier à développer une « approche spécifiquement jungienne ¼ à la psychothérapie assistée par des drogues psychédéliques ­ et il souligne un lien entre l'initiative de Sandison et The Society of Analytical Psychology (SAP) par l'implication de deux de ses membres : Margot Cutner, collègue de Sandison, et Michael Fordham, qui supervisa un candidat sur son travail avec un des anciens patients de Sandison. Malgré les objections de Jung sur l'utilisation des drogues psychédéliques, Sandison et Cutner ont développé des protocoles très innovants durant les années 1950 et furent parmi les premiers à documenter le phénomène de la « renaissance spirituelle symbolisée par l'expérience de naissance, bien connue par la plupart des thérapeutes utilisant le L.S.D. ¼ (Sandison, 2001). Dans deux articles apparentés j'examine la manière dont Jung a traité le motif de la renaissance dans son commentaire sur Le Livre des Morts Tibétain, qui devint par la suite un texte central dans le mouvement psychédélique, et je retrace l'évolution dans la recherche sur les drogues psychédéliques à partir d'une association avec la schizophrénie dans les années 1950 et jusqu'aux paradigmes mystiques des années 1960 et au­delà.

C. G. Jung escribió muy poco sobre las drogas psicodélicas y adoptó una postura escéptica hacia ellas. Sin embargo, quedó lo suficientemente impresionado por el relato, Las Puertas de la Percepción, que Aldous Huxley hizo en 1954 en referencia a su consumo de mescalina, como para invitar a Huxley a visitarle en Suiza. Huxley declinó la invitación, pero en su lugar Jung se reunió con Humphry Osmond, colaborador de Huxley. Este artículo documenta el contacto de Jung con los pioneros británicos en investigación psicodélica y presenta el escaso material que da cuenta de las opiniones de estos, sobre dichas drogas. También determina los esfuerzos del psiquiatra británico Ronald Sandison, que fue el primero en desarrollar un "enfoque explícitamente Junguiano" de la psicoterapia asistida por psicodélicos (Hill, 2013), y destaca una conexión entre la iniciativa de Sandison y la Sociedad de Psicología Analítica (SAP) a través de la participación de dos miembros de la SAP: Margot Cutner, colega de Sandison, y Michael Fordham, quien supervisaba a un candidato a analista que trabajaba con uno de los antiguos pacientes de Sandison. A pesar de las objeciones de Jung al uso de psicodélicos, Sandison y Cutner desarrollaron innovadores protocolos durante la década de 1950 y fueron los primeros en documentar el fenómeno del "renacimiento espiritual simbolizado en la experiencia del nacimiento conocida por muchos terapeutas del LSD" (Sandison, 2001). En dos artículos complementarios, considero el tratamiento que Jung da al motivo del renacimiento en su comentario sobre El Libro Tibetano de los Muertos, que más tarde se convirtió en un texto central del movimiento psicodélico, y trazo la evolución de la investigación sobre psicodélicos desde su asociación con la esquizofrenia durante la década de 1950 hasta los paradigmas místicos de la década de 1960 y posteriores.

Evaluating the complement C1q levels in serum and cerebrospinal fluid in multiple sclerosis patients: Could it serve as a valuable marker in clinical practice?

Immunohistochemical studies have identified complement component C1q in MS lesions. We aimed to compare serum (sC1q) and CSF (csfC1q) levels in a large cohort of MS patients (pwMS) (n = 222) with those of healthy controls (HC, n = 52), individuals with other immune (IND, n = 14), and non-immune neurological disorders (nIND, n = 15), and to analyze their correlation with other biomarkers. pwMS were divided into three series based on their origin. CSF samples were unavailable for HC. All three pwMS cohorts had lower sC1q levels compared to HC and IND. csfC1q was higher in one pwMS cohort, with a trend in another, and correlated with IgG, Free Kappa Light Chains, GFAP, and Chitinase-3 Like Protein-1 in CSF. Our findings suggest a significant role for C1q in MS pathophysiology, potentially serving as a biomarker for disease identification.

O-GlcNAcylation determines the function of the key O-GalNAc glycosyltransferase C1GalT1 in bladder cancer.

Protein glycosylation is a type of protein post-translational modification. One specific example is the modification of proteins with O-linked ß-N-acetylglucosamine (O-GlcNAc) and O-linked α-N-acetylgalactosamine (O-GalNAc). Enhanced levels of both O-GalNAc and O-GlcNAc in bladder cancer (BlCa) have been reported previously. However, the interplay between O-GalNAc and O-GlcNAc has yet to be explored. Herein, we find that the expression level of core1 ß-1,3-galactosyltransferase (C1GalT1), which is responsible for extending and maturing mucin-type O-glycans, is increased in BlCa. This increase is accompanied by O-GlcNAc modification of C1GalT1. This modification stabilizes C1GalT1 expression and strengthens its interaction with its chaperone Cosmc. Mutation at Thr229 or Thr233 attenuates C1GalT1 stability and facilitates its degradation via the proteasome pathway. Furthermore, a decrease in C1GalT1 inhibits the pro-tumorigenic effect on bladder cancer cells by suppressing glycolysis.

Acute Abdominal Pain as the Initial Presentation of an Acquired C1 Inhibitor Deficiency.

Introduction: Acquired angioedema (AAE), a rare cause of adult-onset non-urticarial mucocutaneous angioedema, can present as acute abdomen, a frequent complaint in the emergency room (ER), often leading to unnecessary and potentially harmful procedures. Case Presentation: We report a 47-year-old hypertense male, controlled with an angiotensin converting enzyme inhibitor (ACEI), who presented in the ER with progressively worsening abdominal pain, nausea, and vomiting, and a radiologic workup revealing small intestine thickening, initially diagnosed with ACEI-induced angioedema. However, further investigation revealed low serum levels of C4, C1q, and C1 inhibitors, with an abnormal function of the latter, favoring the diagnosis of AAE instead. The frequent association of this condition with lymphoproliferative disorders encouraged further studies, which unveiled a monoclonal gammopathy IgM/Kappa, representing an increased risk of Waldenström macroglobulinemia, non-Hodgkin lymphoma, and multiple myeloma. Discussion: AAE should be regarded as an important differential diagnosis in patients presenting with acute abdomen in the ER, especially when more common causes are excluded. A correct and early diagnosis may represent a chance for a better prognosis of underlying diseases.

Introdução: O angioedema adquirido (AA), causa rara de angioedema mucocutâneo não urticariforme de início tardio, pode ter como apresentação inicial abdómen agudo, motivo frequente de admissão no serviço de urgência (SU), promovendo frequentemente procedimentos desnecessários e potencialmente prejudiciais. Apresentação do caso: Um homem de 47 anos, hipertenso e controlado com um inibidor da enzima conversora de angiotensina (IECA), recorreu ao SU por um quadro de dor abdominal com agravamento progressivo, náuseas e vómitos. A investigação radiológica inicial revelou espessamento do intestino delgado, culminando num diagnóstico preliminar de angioedema induzido por IECA. No entanto, uma investigação mais aprofundada em regime ambulatório revelou níveis séricos reduzidos de C4, C1q e de inibidor de C1, com função anormal deste último, favorecendo o diagnóstico de AA. A associação frequente desta condição com distúrbios linfoproliferativos incentivou investigação adicional, que revelou uma gamopatia monoclonal IgM/Kappa, representando um risco aumentado de macroglobulinemia de Waldenström, linfoma não-Hodgkin e mieloma múltiplo. Discussão: O AA deve ser considerado um diagnóstico diferencial de abdómen agudo, principalmente após exclusão de causas mais frequentes. Um diagnóstico precoce pode contribuir para um melhor prognóstico da patologia subjacente.

An Immunohistochemical Study of MAGE Proteins in Hepatocellular Carcinoma.

Hepatocellular carcinoma (HCC) is one the most common primary malignancies with high mortality and morbidity. The melanoma-associated antigen (MAGE) gene family includes several genes that are highly expressed in numerous human cancers, making many of them part of the cancer-testis antigen (CTA) family. MAGE-C1 is expressed in various malignancies but is absent in normal cells, except for the male germ line. Its presence is associated with a worse prognosis, increased tumor aggressiveness, and lymph node invasion. Similarly, MAGE-C2 is linked to the development of various malignant tumors. Despite these associations, the roles and mechanisms of MAGE-C1/MAGE-C2 in HCC remain unclear. This study aimed to evaluate the expression of MAGE-C1 and MAGE-C2 in HCC and correlate it with clinicohistological characteristics. Our findings indicated that MAGE-C1 expression is associated with a higher number of nodules, elevated AFP levels, HBV or HCV positivity, older age, male sex, and lymph node invasion. MAGE-C2 expression was correlated with these characteristics and the presence of cirrhosis. These results align with the limited literature, which suggests a correlation between MAGE expression and older age and HBV infection. Consequently, our study suggests that MAGE-C1 and MAGE-C2 are promising novel biomarkers for prognosis and potential therapeutic targets in HCC.

The Regulation of Frontal Cortex Cholesterol Metabolism Abnormalities by NR3C1/NRIP1/NR1H2 Is Involved in the Occurrence of Stress-Induced Depression.

Stress-induced alterations in central neuron metabolism and function are crucial contributors to depression onset. However, the metabolic dysfunctions of the neurons associated with depression and specific molecular mechanisms remain unclear. This study initially analyzed the relationship between cholesterol and depression using the NHANES database. We then induced depressive-like behaviors in mice via restraint stress. Applying bioinformatics, pathology, and molecular biology, we observed the pathological characteristics of brain cholesterol homeostasis and investigated the regulatory mechanisms of brain cholesterol metabolism disorders. Through the NHANES database, we initially confirmed a significant correlation between cholesterol metabolism abnormalities and depression. Furthermore, based on successful stress mouse model establishment, we discovered the number of cholesterol-related DEGs significantly increased in the brain due to stress, and exhibited regional heterogeneity. Further investigation of the frontal cortex, a brain region closely related to depression, revealed stress caused significant disruption to key genes related to cholesterol metabolism, including HMGCR, CYP46A1, ACAT1, APOE, ABCA1, and LDLR, leading to an increase in total cholesterol content and a significant decrease in synaptic proteins PSD-95 and SYN. This indicates cholesterol metabolism affects neuronal synaptic plasticity and is associated with stress-induced depressive-like behavior in mice. Adeno-associated virus interference with NR3C1 in the prefrontal cortex of mice subjected to short-term stress resulted in reduced protein levels of NRIP1, NR1H2, ABCA1, and total cholesterol content. At the same time, it increased synaptic proteins PSD95 and SYN, effectively alleviating depressive-like behavior. Therefore, these results suggest that short-term stress may induce cholesterol metabolism disorders by activating the NR3C1/NRIP1/NR1H2 signaling pathway. This impairs neuronal synaptic plasticity and consequently participates in depressive-like behavior in mice. These findings suggest that abnormal cholesterol metabolism in the brain induced by stress is a significant contributor to depression onset.