Impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients with acute gastrointestinal bleeding: an international multicenter study.

OBJECTIVES: Peptic ulcer is the most common source of non-variceal bleeding. However, it remains controversial whether the outcomes of cirrhotic patients with peptic ulcer bleeding differ from those with variceal bleeding. METHODS: Cirrhotic patients with acute gastrointestinal bleeding (AGIB) who underwent endoscopy and had an identifiable source of bleeding were retrospectively screened from an international multicenter cohort. Logistic regression analyses were performed to explore the impact of peptic ulcer bleeding on in-hospital death and 5-day failure to control bleeding. Propensity score matching (PSM) analysis was performed by matching age, gender, Child-Pugh score, and model for end-stage liver disease score between the peptic ulcer bleeding and variceal bleeding groups. RESULTS: Overall, 1535 patients were included, of whom 73 (4.7%) had peptic ulcer bleeding. Multivariate logistic regression analyses showed that peptic ulcer bleeding was not independently associated with in-hospital death (OR = 2.169, p = 0.126) or 5-day failure to control bleeding (OR = 1.230, p = 0.680). PSM analyses demonstrated that both in-hospital mortality (9.7% vs. 6.3%, p = 0.376) and rate of 5-day failure to control bleeding (6.9% vs. 5.4%, p = 0.787) were not significantly different between the two groups. CONCLUSIONS: The impact of peptic ulcer bleeding on the in-hospital outcomes of cirrhotic patients is similar to that of variceal bleeding.

In this international multicenter study, we included 1535 patients with acute gastrointestinal bleeding (AGIB) and divided them into peptic ulcer bleeding and variceal bleeding groups. We found that only a minority of AGIB episodes in cirrhotic patients was attributed to peptic ulcer. Additionally, after adjusting for the severity of liver dysfunction, the in-hospital mortality and the rate of 5-day failure to control bleeding should be similar between cirrhotic patients with peptic ulcer bleeding and those with variceal bleeding.

Nano-enabled regulation of DNA damage in tumor cells to enhance neoantigen-based pancreatic cancer immunotherapy.

Low-expression antigens, especially neoantigens, pose a significant challenge in immunotherapy for low immunogenicity pancreatic cancer. Increasing the tumor mutation burden is crucial to enhance the expression of tumor antigens and improve tumor immunogenicity. However, the incomplete intervention in DNA stability hampers effective elevation of the tumor mutation burden, thus reducing the probability of neoantigen. To address this issue, we have developed a novel nano-regulator that intervenes in the DNA stability of tumor cells, thereby enhancing tumor mutations. This nano-regulator comprises metal-organic frameworks (MOFs) encapsulating DNA damage agent doxorubicin and DNA damage repair inhibitor siRNA-ATR, enabling simultaneous induction of DNA mutations and inhibition of their repair. Importantly, this regulator, named as MOFDOX&siATR, can modulate the tumor gene expression profile, induce the production of neoantigens of Atp8b1, and enhance the immunogenicity of pancreatic cancer. The characteristics of DNA stability intervention by MOFDOX&siATR hold promise for augmenting the immune response in low immunogenic tumors, making it a potential nanomedicine for the treatment of pancreatic cancer.

Chronic kidney disease and pulmonary hypertension: Progress in diagnosis and treatment.

Pulmonary hypertension (PH) is a medical condition characterized by elevated pulmonary vascular resistance and pressure, resulting from different diseases. Due to their high occurrence of PH, intricate hemodynamic classification, and frequently multifactorial cause and mechanism, individuals suffering from chronic kidney disease (CKD) are categorized as the fifth primary group of PH. Based on both domestic and international research, this article provides information on the epidemiology, risk factors, pathogenesis, and targeted drug treatment of PH associated with CKD.

Engineering Efferocytosis-Mimicking Nanovesicles to Regulate Joint Anti-Inflammation and Peripheral Immunosuppression for Rheumatoid Arthritis Therapy.

Rheumatoid arthritis (RA) is an autoimmune disorder characterized by chronic inflammation of the synovial joints and the dysfunction of regulatory T cells (Tregs) in the peripheral blood. Therefore, an optimal treatment strategy should aim to eliminate the inflammatory response in the joints and simultaneously restore the immune tolerance of Tregs in peripheral blood. Accordingly, we developed an efferocytosis-mimicking nanovesicle that contains three functional factors for immunomodulating of efferocytosis, including "find me" and "eat me" signals for professional (macrophage) or non-professional phagocytes (T lymphocyte), and "apoptotic metabolite" for metabolite digestion. We showed that efferocytosis-mimicking nanovesicles targeted the inflamed joints and spleen of mice with collagen-induced arthritis, further recruiting and selectively binding to macrophages and T lymphocytes to induce M2 macrophage polarization and Treg differentiation and T helper cell 17 (Th17) recession. Under systemic administration, the efferocytosis-mimicking nanovesicles effectively maintained the pro-inflammatory M1/anti-inflammatory M2 macrophage balance in joints and the Treg/Th17 imbalance in peripheral blood to prevent RA progression. This study demonstrates the potential of efferocytosis-mimicking nanovesicles for RA immunotherapy.

Signature and function of plasma exosome-derived circular RNAs in patients with hypertensive intracerebral hemorrhage.

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.

Investigation on the Osteogenic and Antibacterial Properties of Silicon Nitride-Coated Titanium Dental Implants.

The silicon nitride (Si3N4) coating exhibits promising potential in oral applications due to its excellent osteogenic and antibacterial properties. However, a comprehensive investigation of Si3N4 coatings in the context of dental implants is still lacking, especially regarding their corrosion resistance and in vivo performance. In this study, Si3N4 coatings were prepared on a titanium surface using the nonequilibrium magnetron sputtering method. A systematic comparison among the titanium group (Ti), Si3N4 coating group (Si3N4-Ti), and sandblasted and acid-etched-treated titanium group (SLA-Ti) has been conducted in vitro and in vivo. The results showed that the Si3N4-Ti group had the best corrosion resistance and antibacterial properties, which were mainly attributed to the dense structure and chemical activity of Si-O and Si-N bonds on the surface. Furthermore, the Si3N4-Ti group exhibited superior cellular responses in vitro and new bone regeneration and osseointegration in vivo, respectively. In this sense, silicon nitride coating shows promising prospects in the field of dental implantology.

Design and Synthesis of C4-Symmetric Axially Chiral ß-Aryl Porphyrins and Application for Supporting Ir(III)-Catalyzed Enantioselective C-H Alkylation.

A hitherto unknown class of C4-symmetric Caryl-Cß (C3, C8, C13, C18) axially chiral porphyrins has been synthesized and the application of their iridium (Ir) complexes in catalytic asymmetric C(sp3)-H functionalization is documented. Cyclotetramerization of enantioenriched axially chiral 2-hydroxymethyl-3-naphthyl pyrroles under mild acidic conditions affords, after oxidation with 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), the C4-symmetric α,α,α,α-atropenantiomer as an only isolable diastereomer. Both regioisomeric Ir(Por*)(CO)(Cl) complexes catalyze the carbene C-H insertion reaction affording the same enantiomer, albeit with slight difference in enantioselectivity. With the optimum Ir-complex 3 e, the 2-substituted arylacetic acid derivatives were generated from diazo compounds and cyclohexadiene in excellent yields and enantioselectivities.

Immunosuppressive microvesicles-mimetic derived from tolerant dendritic cells to target T-lymphocytes for inflammation diseases therapy.

The utilization of extracellular vesicles (EV) in immunotherapy, aiming at suppressing peripheral immune cells responsible for inflammation, has demonstrated significant efficacy in treating various inflammatory diseases. However, the clinical application of EV has faced challenges due to their inadequate targeting ability. In addition, most of the circulating EV would be cleared by the liver, resulting in a short biological half-life after systemic administration. Inspired by the natural microvesicles (MV, as a subset of large size EV) are originated and shed from the plasma membrane, we developed the immunosuppressive MV-mimetic (MVM) from endotoxin tolerant dendritic cells (DC) by a straightforward and effective extrusion approach, in which DC surface proteins were inherited for providing the homing ability to the spleen, while αCD3 antibodies were conjugated to the MVM membranes for specific targeting of T cells. The engineered MVM carried a large number of bioactive cargos from the parental cells, which exhibited a remarkable ability to promote the induction of regulatory T cells (Treg) and polarization of anti-inflammatory M2 macrophages. Mechanistically, the elevated Treg level by MVM was mediated due to the upregulation of miR-155-3p. Furthermore, it was observed that systemic and local immunosuppression was induced by MVM in models of sepsis and rheumatoid arthritis through the improvement of Treg and M2 macrophages. These findings reveal a promising cell-free strategy for managing inflammatory responses to infections or tissue injury, thereby maintaining immune homeostasis.

METTL3-mediated methylation of CYP2C19 mRNA may aggravate clopidogrel resistance in ischemic stroke patients.

Background: N6-methyladenosine (m6A) is the most frequently occurring interior modification in eukaryotic messenger RNA (mRNA), and abnormal mRNA modifications can affect many biological processes. However, m6A's effect on the metabolism of antiplatelet drugs for the prevention of ischemic stroke (IS) remains largely unclear. Methods: We analyzed the m6A enzymes and m6A methylation in peripheral blood samples of IS patients with/without clopidogrel resistance (CR), and the peripheral blood and liver of rat models with/without CR. We also compared the effect of m6A methylation on the expression of the drug-metabolizing enzymes (CYP2C19 and CYP2C6v1) in CR and non-CR samples. Results: Methyltransferase-like 3 (METTL3), an m6A enzyme, was highly expressed in the peripheral blood of patients with CR, and in both the peripheral blood and liver of rats with CR. This enzyme targets CYP2C19 or CYP2C6v1 mRNA through m6A methylation, resulting in low expression of CYP2C19 or CYP2C6v1 mRNA. Consequently, this leads to decreased clopidogrel metabolism and CR. Conclusion: The METTL3-mediated methylation of CYP2C19 mRNA may aggravate CR in IS patients.

Knockdown of circ_0044226 promotes endoplasmic reticulum stress-mediated autophagy and apoptosis in hepatic stellate cells via miR-4677-3p/SEC61G axis.

Downregulation of circ_0044226 has been demonstrated to reduce pulmonary fibrosis, but the role of circ_0044226 in liver fibrosis remains to be explored. In this work, we found that circ_0044226 expression was upregulated during liver fibrosis. Knockdown of circ_0044226 inhibited proliferation, promoted autophagy and apoptosis of hepatic stellate cell LX-2. Bioinformatic analysis and dual luciferase reporter assays confirmed the interaction between circ_0044226, miR-4677-3p and SEC61G. Mechanistically, knockdown of circ_0044226 suppressed SEC61G expression by releasing miR-4677-3p, thereby enhancing endoplasmic reticulum stress. Overexpression of SEC61G or endoplasmic reticulum stress inhibitor 4-phenylbutiric acid partially reversed the effect of knockdown circ_0044226 on LX-2 cell function. In vivo experiments showed that inhibition of circ_0044226 attenuated CCL4-induced liver fibrosis in mice. These imply that circ_0044226 may be a potential target for the treatment of liver fibrosis.

Inhibiting the MAPK pathway improves heart failure with preserved ejection fraction induced by salt-sensitive hypertension.

Heart failure (HF) preserved ejection fraction (HFpEF) accounts for almost 50% of HF, and hypertension is one of the pathogenies. The MAPK signaling pathway is closely linked to heart failure and hypertension; however, its function in HEpEF resulting from salt-sensitive hypertension is not well understood. In this work, a salt-sensitive hypertension-induced HEpEF model was established based on deoxycorticosterone acetate-salt (DOCA-salt) hypertension mice. The impact of the MAPK inhibitor (Doramapimod) on HEpEF induced by salt-sensitive hypertension was assessed through various measures, such as blood pressure, transthoracic echocardiography, running distance, and histological analysis, to determine its therapeutic effectiveness on cardiac function. In addition, the effects of high salt on myogenic cells were also evaluated in vitro using qRTPCR. The LV ejection fractions (LVEF) in DOCA-salt hypertension mice were over 50%, indicating that the salt-sensitive hypertension-induced HFpEF model was successful. RNA-seq revealed that the MAPK signaling pathway was upregulated in the HFpEF model compared with the normal mice, accompanied by hypertension, impaired running distance, restricted cardiac function, increased cross-sectional and fibrosis area, and upregulation of heart failure biomarkers, including GAL-3, LDHA and BNP. The application of Doramapimod could improve blood pressure, cardiomyocyte hypertrophy, and myocardial fibrosis, as well as decrease the aforementioned heart failure biomarkers. The qRTPCR results showed similar findings to these observations. Our findings suggest that the use of a MAPK inhibitor (Doramapimod) could be a potential treatment for salt-sensitive hypertension-induced HFpEF.

Human Adipose Tissue Lysate-Based Hydrogel for Lasting Immunomodulation to Effectively Improve Spinal Cord Injury Repair.

The long-term inflammatory microenvironment is one of the main obstacles to inhibit acute spinal cord injury (SCI) repair. The natural adipose tissue-derived extracellular matrix hydrogel shows effective anti-inflammatory regulation because of its unique protein components. However, the rapid degradation rate and removal of functional proteins during the decellularization process impair the lasting anti-inflammation function of the adipose tissue-derived hydrogel. To address this problem, adipose tissue lysate provides an effective way for SCI repair due to its abundance of anti-inflammatory and nerve regeneration-related proteins. Thereby, human adipose tissue lysate-based hydrogel (HATLH) with an appropriate degradation rate is developed, which aims to in situ long-term recruit and induce anti-inflammatory M2 macrophages through sustainedly released proteins. HATLH can recruit and polarize M2 macrophages while inhibiting pro-inflammatory M1 macrophages regardless of human or mouse-originated. The axonal growth of neuronal cells also can be effectively improved by HATLH and HATLH-induced M2 macrophages. In vivo experiments reveal that HATLH promotes endogenous M2 macrophages infiltration in large numbers (3.5 × 105/100 µL hydrogel) and maintains a long duration for over a month. In a mouse SCI model, HATLH significantly inhibits local inflammatory response, improves neuron and oligodendrocyte differentiation, enhances axonal growth and remyelination, as well as accelerates neurological function restoration.

Bomidin attenuates inflammation of periodontal ligament stem cells and periodontitis in mice via inhibiting ferroptosis.

AIM: Periodontitis is a prevalent oral immunoinflammatory condition that is distinguished by the compromised functionality of periodontal ligament stem cells (PDLSCs). Bomidin, a new recombinant antimicrobial peptide (AMP), exhibits antibacterial properties and modulates immune responses. Nevertheless, the precise anti-inflammatory impact of bomidin in periodontitis has yet to be fully elucidated. Thus, the study aimed to clarified the role of bomidin in modulating inflammation and its underlying mechanisms. METHODS: TNF-α was applied to treating PDLSCs for establishing a cell model of periodontitis. Bomidin, RSL3, ML385 and cycloheximide were also used to treat PDLSCs. Transcriptome sequencing, RT-qPCR, western blot, immunofluorescence, immunohistochemistry, Fe2+ detection probe, molecular docking, Co-IP assay, ubiquitination assay and murine models of periodontitis were used. RESULTS: Our study demonstrated that bomidin effectively suppressed inflammation in PDLSCs stimulated by TNF-α, through down-regulating the MAPK and NF-κB signaling pathways. Furthermore, bomidin exerted inhibitory effects on ferroptosis and activated the Keap1/Nrf2 pathway in the TNF-α group. There is a strong likelihood of bonding bomidin with Keap1 protein, which facilitated the degradation of Keap1 protein via the ubiquitin-proteasome pathway, leading to an enhanced translocation of Nrf2 protein to the nucleus. CONCLUSIONS: Bomidin can directly bond to Keap1 protein, resulting in the degradation of Keap1 through the ubiquitin-proteasome pathway, thereby further activating the Keap1/Nrf2 pathway. The upregulation of the Keap1/Nrf2 signaling pathway was found to contribute to the suppression of ferroptosis, ultimately alleviating inflammation in treatment of periodontitis.

Association of serum Asprosin concentrations with heart failure.

BACKGROUND: To analyze the association of serum Asprosin concentrations with heart failure (HF). METHODS: A total of 103 patients with HF were included in the HF group, and 103 patients with health checkups were included in the non-HF group. The serum Asprosin levels of the two groups were measured, and relevant clinical data were collected for statistical analysis. RESULTS: Compared with the non-HF group, the serum Asprosin concentration was significantly higher in the HF group, and the difference was statistically significant (P < 0.001). According to the serum Asprosin levels, we divided all the subjects into three quartiles. We found that the prevalence of HF increased with increasing serum Asprosin levels in the three groups (P < 0.001). Serum Asprosin levels were positively correlated with NT-ProBNP (P < 0.05) and negatively correlated with LVEF (P < 0.001). Dichotomous logistic regression analysis found Asprosin and age to be independent risk factors for HF (OR = 1.010, 95% CI: 1.003-1.018; OR = 1.058, 95% CI:1.004-1.665, respectively). Combining Asprosin and NT-proBNP indicators to draw ROC curves can improve the specificity and sensitivity of HF diagnosis. CONCLUSIONS: Serum Asprosin levels were significantly elevated in HF patients. The serum Asprosin level is an independent risk factor for HF, and the combined detection of Asprosin and NT-proBNP levels can improve the accuracy of HF diagnosis.

Internet use and depressive symptoms among Chinese older adults: Two sides of internet use.

Objective: To explore the relationship between internet use which includes time spent on the internet, internet skills, types of online activities, and depressive symptoms in older adults. Methods: We used 2020 China Family Panel Studies (CFPS) data with 3,171 older adults aged 60 years. Depression symptoms were measured with the Center for Epidemiologic Studies Depression (CES-D), and internet use was measured by time spent on the internet, internet skills, and types of online activities. Multiple linear regression models were used to explore the relationship between internet use and depressive symptoms in older adults. Results: Longer time spent on the internet was associated with higher scores of depressive symptoms (ß = 0.14). Higher internet skills were associated with lower scores of depressive symptoms (ß = -0.42). Watching short-form videos (ß = 1.34) was associated with higher depressive symptom scores, and the use of the WeChat function (ß = -0.96) was associated with lower depressive symptom scores, while online games and online shopping were not significant. Conclusion: The effect of internet use on depressive symptoms in older adults is a double-edged sword. Controlling the time spent on the internet, improving internet skills, and guiding specific a type of online activities in older adults can improve depressive symptoms through rational use.

Lactobacillus plantarum-Derived Postbiotics Ameliorate Acute Alcohol-Induced Liver Injury by Protecting Cells from Oxidative Damage, Improving Lipid Metabolism, and Regulating Intestinal Microbiota.

Here, the aim was to evaluate the protective effect of Lactobacillus plantarum-derived postbiotics, i.e., LP-cs, on acute alcoholic liver injury (ALI). After preincubation with LP-cs, HL7702 human hepatocytes were treated with alcohol, and then the cell survival rate was measured. C57BL/6 male mice were presupplemented with or without LP-cs and LP-cs-loaded calcium alginate hydrogel (LP-cs-Gel) for 3 weeks and given 50% alcohol gavage to establish the mouse model of ALI, LP-cs presupplementation, and LP-cs-Gel presupplementation. The histomorphology of the liver and intestines; the levels of serum AST, ALT, lipid, and SOD activity; liver transcriptomics; and the metagenome of intestinal microbiota were detected in all mouse models. In vitro, LP-cs significantly increased the survival rate of alcohol-treated cells. In vivo, presupplementation with LP-cs and LP-cs-Gel restored the levels of serum AST, ALT, and SOD activity, as well as TC and TG, after acute alcohol intake. In the LP-cs-presupplemented mice, the genes involved in fatty acid metabolic processes were upregulated and the genes involved in steroid biosynthesis were downregulated significantly as compared with the ALI mice. LP-cs significantly increased the abundance of intestinal microbiota, especially Akkermansia muciniphila. In conclusion, LP-cs ameliorates ALI by protecting hepatocytes against oxidative damage, thereby, improving lipid metabolism and regulating the intestinal microbiota. The effect of LP-cs-Gel is similar to that of LP-cs.

Geraniol prevents Helicobacterium pylori-induced human gastric cancer signalling by enhancing peroxiredoxin-1 expression in GES-1 cells.

Helicobacter pylori (H. pylori), a gram-negative bacterial microbiological carcinogen, has been identified as the leading jeopardy feature for developing human gastric cancer (GC). As a result, inhibiting H. pylori growth has been identified as an effective and critical technique for preventing GC development. In this study, geraniol inhibits H. pylori-induced gastric carcinogen signalling in human gastric epithelial cells (GES-1). Geraniol prevents cytotoxicity, ROS and apoptosis in H. pylori-induced GES-1 cells. Furthermore, geraniol protects against H. -induced antioxidant depletion caused by malondialdehyde, damage of reactive DNA and nuclear fragmentation. Geraniol significantly reduced the expression of phosphorylated mitogen activated protein kinases (MAPKs) proteins such as p38 MAPK, extracellular signal-regulated kinase-1 (ERK1), c-Jun N-terminal kinase (c-JNK), tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), and cyclooxygenase-2 (COX-2) in GES-1 infected with H. pylori. Furthermore, geraniol increased the antioxidant protein peroxiredoxin-1 (Prdx-1) in H. pylori-infected cells. Geraniol thus protects H. pylori-concomitant infection, and its resistance may be a possible method in preventing gastric cancer caused by H. pylori.

Correlation of patients' demographics and clinical symptoms with temporomandibular disorders.

OBJECTIVE: To investigate the correlation between basic characteristics and clinical features of patients with temporomandibular disorders (TMD). METHODS: The R language statistical tool was used to analyze the clinical information of 500 TMD patients, i.e., age, sex, joint noises, mouth opening pattern, and pain symptoms, as well as the results of the mandibular push-back test. A pairwise correlation analysis of each clinical feature was carried out. RESULTS: The highest incidence of TMD was observed in the age group of 20 to 30 years (240/500). Around 2/3 of the patients showed pain symptoms. Abnormal mouth opening patterns, joint noises, and temporomandibular joint synovitis (TMJS) were observed in 48.4, 65.4, and 34% of patients, respectively. CONCLUSION: Joint click and the corrected deviation of the mouth opening pattern are signs of early-stage TMD, whereas limited mouth opening and TMJS are indicators of progressive stage and complicated TMD.

Genetic and Pharmacological Inhibition of Astrocytic Mysm1 Alleviates Depressive-Like Disorders by Promoting ATP Production.

Major depressive disorder (MDD) is a leading cause of disability worldwide. A comprehensive understanding of the molecular mechanisms of this disorder is critical for the therapy of MDD. In this study, it is observed that deubiquitinase Mysm1 is induced in the brain tissues from patients with major depression and from mice with depressive behaviors. The genetic silencing of astrocytic Mysm1 induced an antidepressant-like effect and alleviated the osteoporosis of depressive mice. Furthermore, it is found that Mysm1 knockdown led to increased ATP production and the activation of p53 and AMP-activated protein kinase (AMPK). Pifithrin α (PFT α) and Compound C, antagonists of p53 and AMPK, respectively, repressed ATP production and reversed the antidepressant effect of Mysm1 knockdown. Moreover, the pharmacological inhibition of astrocytic Mysm1 by aspirin relieved depressive-like behaviors in mice. The study reveals, for the first time, the important function of Mysm1 in the brain, highlighting astrocytic Mysm1 as a potential risk factor for depression and as a valuable target for drug discovery to treat depression.

Role of 5-HT2A Receptor in Modulating Glutamatergic Activity in the Ventrolateral Orbital Cortex: Implication in Trigeminal Neuralgia.

5-HT2A receptors (5-HT2ARs) are widely expressed in the central nervous system, including in the ventrolateral orbital cortex (VLO). The VLO is an important cortical component for pain processing. Brain 5-HT2ARs are implicated in both pro- and anti- nociceptive functions. However, the roles of 5-HT2ARs in the VLO in trigeminal neuralgia and neuronal synaptic function remain to be understood. We used chronic constriction injury of infraorbital nerve (IoN-CCI) model and shRNA mediated gene knockdown in mice to investigate the role of 5-HT2ARs in the VLO in trigeminal neuralgia. We found that knockdown of 5-HT2ARs in the VLO aggravated spontaneous pain and mechanical allodynia in mice after IoN-CCI. At the synaptic level, decreasing 5-HT2AR expression by shRNA or inhibition of 5-HT2AR activity by its antagonist ketanserin decreased the frequency and amplitude of spontaneous excitatory postsynaptic currents (sEPSCs) of the neurons in the VLO, whereas 5-HT2AR partial agonist 2,5-Dimethoxy-4-iodoamphetamine (DOI) enhanced sEPSCs of the neurons in the VLO. In summary, 5-HT2ARs in the VLO modulate the trigeminal pain by regulating neuronal glutamatergic activity.