Pathological Symptoms Research Articles

Host-derived Bacillus antagonistic novel duck reovirus infection by regulating gut microbiota-mediated immune responses

The Novel Duck Reovirus (NDRV) infection poses a significant health risk to ducks, primarily attributed to the absence of efficacious preventive measures. This research aimed to investigate whether the administration of isolated Bacillus could protect antagonistic NDRV infection in a Cherry Valley duck model. Four indigenous Bacillus strains from the feces of healthy ducks demonstrated promising biosafety profiles. One-day-old ducklings were inoculated intramuscularly with NDRV and subsequently subjected to a 28-day regimen of mixed Bacillus (Bac) treatment. The effects of Bac on pathological symptoms, immune response and intestinal flora were analyzed. The results showed that Bac significantly reduced weight loss, clinical symptoms, and viral loading. Moreover, Bac treatment significantly decreased neutrophils, monocytes proportion, the TNF-α, IL-1β and IL-6 expression, increased platelets, lymphocytes proportion, the IFN-β and IL-10 expression, and restored immune dysfunction. In addition, Bac has increased the relative abundance of Enterococcaceae, Lactobacillales, Bacilli, Ruminococcaceae, Clostridium and Phascolarctobacterium. Moreover, the metabolism of short-chain fatty acids (SCFAs) was further regulated, thereby enhancing the acetate content. The correlation analysis showed that a positive association between acetate levels and IFN-β expression, while a negative correlation was observed with viral loading. In conclusion, the results suggest that the anti-NDRV mechanism of Bac may involve the modulation of gut microbiota to elicit an immune response that inhibits viral infection. This study presents a novel approach for the prevention and treatment of NDRV, thereby establishing a theoretical foundation for the future development of probiotics in the prevention and treatment of NDRV.

The protective effect of amitriptyline on experimental colitis through inhibiting TLR-4/MD-2 signaling pathway

Amitriptyline, a pleiotropic tricyclic antidepressant, possesses antioxidant and anti-inflammatory properties. Despite its diverse benefits, the specific effects of amitriptyline on inflammatory bowel disease (IBD) are not yet well defined. To explore this, we used a dextran sulfate sodium (DSS)–induced colitis model to examine the anti-inflammatory effects of amitriptyline and the underlying mechanisms by which it operates. Our research revealed that amitriptyline is effective in alleviating several pathological manifestations associated with colitis. This includes improving body weight retention, reducing disease activity index, lessening of colon length shortening, and repairing of colonic mucosal damage. Treatment with amitriptyline significantly protected mucosal injury by preserving the population of goblet cells and increasing the expression of tight junction proteins. Furthermore, we observed that amitriptyline effectively countered immune cell infiltration, specifically neutrophils and macrophages, while simultaneously lowering the levels of inflammatory cytokines such as tumor necrosis factor α, interleukin (IL)-1β, and IL-6. Additionally, RNA sequencing analysis pointed to the potential involvement of the Toll-like receptor (TLR) pathway in the anticolitic effects induced by amitriptyline. Subsequent Western blot analysis indicated that amitriptyline significantly inhibited the TLR-4–mediated nuclear factor (NF)-κB signaling pathway. To bolster our findings, in vitro studies demonstrated that amitriptyline downregulated the TLR-4/NF-κB/mitogen-activated protein kinase signaling cascades in mouse macrophages stimulated with lipopolysaccharide. Further molecular investigations revealed that amitriptyline was able to suppress the elevated expression of myeloid differentiation factor 2 that lipopolysaccharide stimulation typically induces. In summary, our findings suggest that amitriptyline effectively mitigates DSS–induced colitis in mice through the inhibition of TLR-4/myeloid differentiation 2 pathway signaling, indicating its potential repurposing for IBD treatment. Significance StatementThe potential of using amitriptyline in treating inflammatory bowel disease appears promising, leveraging its established safety and dosing profile as an antidepressant. The study results show that amitriptyline can alleviate pathological symptoms, inflammation, and intestinal mucosal damage in mice with colitis induced by DSS. The protective effect observed appears to be linked to the inhibition of TLR-4/myeloid differentiation 2 signaling pathway. By exploring novel applications for existing medications, we can optimize amitriptyline’s efficacy and broaden its impact in both medical and commercial contexts.

CIP2A inhibitors TD52 and Ethoxysanguinarine promote macrophage autophagy and alleviates acute pancreatitis by modulating the AKT-mTOR pathway

BackgroundAcute pancreatitis (AP) is a prevalent and serious condition within the digestive system, with approximately 20 % to 30 % of cases advancing to severe acute pancreatitis (SAP). During the initial phases of SAP, macrophages are activated in response to the substantial amounts of acinar cell contents and damage-associated molecular patterns (DAMPs) resulting from acinar cell destruction. Subsequently, activated macrophages release a significant array of pro-inflammatory factors that exacerbate the progression of SAP. Cancerous inhibitor of protein phosphatase 2A (CIP2A) is an oncogenic protein that is intimately linked to immune regulation. While the role of CIP2A in T-cell-mediated specific immune responses has been reported, its function and mechanism in macrophages, a component of non-specific immunity, have not been widely studied. This research fills this knowledge gap by elucidating the critical role of CIP2A in regulating macrophage autophagy and inflammation. This finding not only expands our understanding of CIP2A in immune modulation but also provides a new scientific basis and potential application prospects for targeting CIP2A in the treatment of AP. MethodsWe established AP using a combination of palmitoleic acid with anhydrous ethanol or using caerulein alone. The effects of TD52 and Ethoxysanguinarine (Etho) on SAP were evaluated through serological, histopathological, and tissue inflammation observations. The effect of TD52 on macrophage activation in vitro was examined using primary macrophages (PMs) and RAW264.7 cells. ResultsWe found that TD52 and Etho inhibit CIP2A expression while reducing the levels of serum amylase, lipase, and inflammatory cytokines, thereby alleviating the pathological symptoms of SAP. Additionally, TD52 could reduce the infiltration of macrophages into pancreatic tissue. Therefore, we established a model of macrophage inflammatory response mimicking the pathophysiological process of AP and detected changes in inflammation, apoptosis, and autophagy through pre-treatment of macrophages with TD52. The results show that inhibiting CIP2A expression decreases the release of inflammatory cytokines and reduces apoptosis in macrophages. Further exploration revealed that TD52 promoted macrophage autophagy regulation and inhibited the AKT-mTOR pathway to modulate macrophage activation. ConclusionIn summary, our findings indicate that TD52 and Etho can alleviate the severity of SAP. TD52 can block the AKT-mTOR pathway to promote macrophage autophagy, thereby improving SAP. Thus, CIP2A may serve as one of the molecular targets in SAP, highlighting its potential as a therapeutic option.

Sanguinarine chloride hydrate mitigates colitis symptoms in mice through the regulation of the intestinal microbiome and metabolism of short-chain fatty acids

Sanguinarine constitutes the main components of Macleaya cordata, and exhibits diverse biological and pharmacological activities. This study investigated the effects of sanguinarine chloride hydrate (SGCH) on dextran sulfate sodium (DSS)-induced ulcerative colitis (UC) mice. Five groups were designed to investigate the effects of SGCH on the pathological symptoms, the mRNA expression levels of inflammatory cytokines, colonic mucosal barrier damage, microbiota composition, and SCFAs metabolism in UC mice. The administration of SGCH in DSS-induced UC mice resulted in the amelioration of pathological symptoms, as evidenced by an increase in body weight, a decrease in disease activity index score, elongation of colon length, reduction in spleen index, and improvement in colon injury. SGCH can regulate the expression of inflammatory cytokines (IL-6, TNF-α, IL-1β and IL-10) and tight junction proteins (ZO-1 and Occludin) associated with UC. SGCH exhibited a significant decrease in NF-κB P65 mRNA expression levels, accompanied by a significantly reduced protein level of NF-κB P-P65/P65. Further studies revealed SGCH effectively reversed the decrease in intestinal microbiota diversity induced by UC, thereby promoting the growth of beneficial bacteria such as Akkermansia, Alistipes, and norank_o_Clostridia_UCG-014. Correlation analysis demonstrated a positive association between butanoic acid, propanoic acid, isobutyric acid, isovaleric acid, valeric acid, hexanoic acid with Colidextribacter, while Coriobacteriaceae_UCG-002 exhibited a negative correlation with butanoic acid, acetic acid and propanoic acid. In conclusion, the administration of SGCH can ameliorate clinical symptoms in UC mice, regulate the expression of inflammatory cytokines and tight junction proteins, modulate intestinal microbiota metabolism and SCFAs production.

Alleviation of ulcerative colitis via curcumin-fortified orange juice: Utilization of orange-derived extracellular vesicles as active nanocarrier

There is evidence that consumption of fruit and vegetable juices may alleviate ulcerative colitis. However, their application is limited because of their relatively weak and uncertain health benefits. In this study, curcumin-fortified orange juice (Cur-OJ) was produced using orange extracellular vesicles as natural active nanocarriers. The concentration, composition, morphology and size of extracellular vesicles were first determined. It was shown that curcumin was incorporated into the lipid bilayer of extracellular vesicles in an amorphous form. The influences of oral administration of Cur-OJ on DSS-triggered colitis mice was evaluated. Cur-OJ reduced the pathological symptoms in mice, affected the expression of inflammatory cytokine, and improved the integrity of the colon tissue through enhancing the levels of three tight junction proteins. The gut microflora and colonic metabolites of colitis mice in Cur-OJ group were close to those in control group. Noticeably, the treatment of colitis was better in the Cur-OJ group than those in curcumin or orange juice groups, suggesting that curcumin and orange juice can work together to relieve colitis symptoms. In summary, this study showed that Cur-OJ can reduce colitis, which may be useful for the progress of novel functional fruit or vegetable juice and foods designed to improve body health and human wellbeing.

Neohesperidin protects against colitis-associated colorectal cancer in mice via suppression of the NF-κB/p65 and MAPK pathways

Patients with inflammatory bowel disease (IBD) are at increased risk of developing colitis-associated colorectal cancer (CAC). Neohesperidin (NHP), a flavanone glycoside derived from citrus fruits, has been reported to have anti-inflammatory, antioxidant, and anticancer potential. However, the function of NHP on tumorigenesis has not been well understood. To investigate the potential chemopreventive effects of NHP on CAC development, an in vivo azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced mouse model was used and NHP was administered by daily gavage for 10 weeks throughout the model period. In this study, we found that NHP effectively ameliorated AOM/DSS-induced pathological symptoms of colitis and thus inhibited colon tumorigenesis in mice. NHP treatment attenuated tumor proliferation, induced apoptosis, and inhibited angiogenesis during CAC development. In addition, NHP inhibited macrophage infiltration and reduced the expression of proinflammatory cytokines such as TNF-α, IL-1β, IL-6, and COX-2 at both mRNA and protein levels, and the higher the concentration of NHP, the better the inhibition. It is worth noting that the positive therapeutic agent mesalazine (100 mg/kg) had a therapeutic effect comparable to that of a low concentration of NHP (50 mg/kg), but less effective than the same concentration of NHP (100 mg/kg). In addition, NHP may exert anti-inflammatory and anticancer effects by inhibiting the NF-κB/p65 and ERK/p38 MAPK pathways. Our findings highlight the potential of NHP as a potential therapeutic candidate for IBD and CAC.

Mindfulness Meditation Improves Mental Health in Flood Survivors and Disaster Volunteers: A Randomized Wait-List Controlled Trial

Abstract Objectives Being affected by a natural disaster or helping victims can impact mental health. This study aimed to examine whether a digital mindfulness intervention positively affects self-compassion, life satisfaction, and positive affect, and alleviates negative affect, perceived stress, and pathological symptoms in victims and volunteers of the flood disaster in Germany in July 2021. Method Participants were 146 people affected by the flood (via house, n = 88; friends, n = 100; workplace, n = 54) and/or volunteered after the disaster (n = 86). After the randomized assignment, 74 received a 6-week application-based mindfulness intervention, and 72 were allocated to the wait-control condition. The control group received the same intervention 6 weeks later. Before (T1) and after (T2) the intervention of the first group and after the intervention of the control group (T3), participants filled out questionnaires regarding different aspects of mental health. Results We found significant interaction effects of time and intervention for all variables (self-compassion, life satisfaction, positive and negative affect, perceived stress, and pathological symptoms), indicating effectiveness of the digital mindfulness intervention. No deterioration were found between T2 and T3 in the intervention group for any of the variables. Conclusions The 6-week digital mindfulness program positively affected the mental health of both disaster victims and volunteers. Therefore, a digital mindfulness intervention could be a good alternative in situations where group programs or face-to-face meetings are infeasible.

Changes in insomnia and binge-eating symptom severity before and after treatment of eating disorders in individuals with non-low-weight binge-spectrum disorders.

Although emerging research suggests insomnia is a significant problem among people with eating disorders, little is known about how insomnia symptoms may serve as risk factors for eating disorder symptoms, treatment outcome, and relapse. University students with non-low-weight eating disorders (N = 89) completed a mobile guided self-help cognitive behavioural intervention for eating disorders. Insomnia and binge-eating symptoms were assessed at pre-treatment and end-of-treatment using the Insomnia Severity Index and Eating Pathology Symptoms Inventory. Multiply imputed datasets were used to test associations between insomnia and binge eating before, during and after treatment. Insomnia was positively associated with binge-eating symptoms prior to treatment (r = 0.47). Baseline insomnia symptoms were associated with binge-eating symptoms at end-of-treatment (est = 0.269). Eating disorder treatment modestly reduced insomnia (d = -0.38); however, about half of people with clinically significant insomnia prior to treatment remained symptomatic. Insomnia symptoms and binge-eating symptoms did not change concurrently during treatment. Overall, results support an association between insomnia and binge eating. Although eating disorder treatment may impact insomnia, many individuals remained symptomatic for sleep problems, suggesting the need for follow-up treatments, such as cognitive behavioural therapy for insomnia, or the development of integrated insomnia-eating disorder treatments. Future studies are needed to examine causal links between insomnia and eating disorder symptoms, and test if insomnia predicts relapse after eating disorder treatment.

Coronary stent migration into the aorta during implantation in the orifice of the right coronary artery and its elimination: Review with a clinical case

The purpose of this study was to analyse a vivid clinical case of problematic stent extraction that migrated during coronary stenting. Materials and methods. The following clinical methods of research were used: general laboratory and instrumental, which were applied in interventional cardiology. Results and discussion. A patient born in 1950 with pronounced symptoms of cardiac pathology was admitted to the cardiology department. The diagnosis of coronary heart disease in the form of class III of angina pectoris was established. Coronary angiography was recommended to the patient, where 3 vascular lesions of the coronary arteries were detected, coronary artery bypass grafting was recommended, which the patient flatly refused. Coronary stenting was performed 2 days later, but a complication occurred during the intervention – stent dislocation and migration during implantation into the mouth of the right coronary artery, which occurred during endovascular interventions for myocardial revascularisation in coronary heart disease. The causes of such complications have been identified, and the endovascular methods used in their treatment have been described. Several attempts have been made to extract the migrated stent, but the first of them were unsuccessful. Only after 5 attempts to remove the migrated stent using the ONE SNARE endovascular trap was success achieved. Conclusions. The article provides a comprehensive analysis of the problem of stent migration in various vascular systems and organs, emphasizing the seriousness and complexity of this phenomenon. It demonstrates the importance of timely diagnosis and discusses treatment approaches that can reduce the risk of complications and improve patient outcomes.

Multi-omics analyses of Bacillus amyloliquefaciens treated mice infected with Schistosoma japonicum reveal dynamics change of intestinal microbiome and its associations with host metabolism.

Schistosomiasis japonica is a serious threat to human health. It causes damage to the intestine and liver. Probiotic therapy has been shown to be effective in alleviating intestinal diseases and improving host health. Previous studies have found that Bacillus amyloliquefaciens could alleviate the pathological symptoms of schistosomiasis japonica, but the regulatory mechanism of alleviating schistosomiasis japonica is still unknown. This study analyzed the dynamic changes of intestinal microbiome in mice infected with Schistosoma japonicum after the intervention of B. amyloliquefaciens and its connection to host metabolism by multi-omics sequencing technology. B. amyloliquefaciens was found to significantly regulate the homeostasis of intestinal microbiota by promoting the growth of beneficial bacteria and inhibiting potential pathogenic bacteria and protect the number of core microbes. Meanwhile, the genes related to the metabolism of glycerophospholipids and amino acid from intestinal microbiome changed significantly, and were shown to be significantly positively correlated with the associated metabolites of microbial origin. Moreover, host metabolism (lipid metabolism and steroid hormone biosynthesis) was also found to be significantly regulated. The recovery of intestinal microbial homeostasis and the regulation of host metabolism revealed the potential probiotic properties of B. amyloliquefaciens, which also provided new ideas for the prevention and adjuvant treatment of schistosomiasis japonica.

Chicoric acid exerts therapeutic effects in DSS-induced ulcerative colitis by targeting the USP9X/IGF2BP2 axis.

Chicoric acid, a hydroxycinnamic acid, exhibits anti-inflammation activities. However, the specific mechanisms underlying the effects of chicoric acid on dextran sulfate sodium (DSS)-induced colitis remain unclear. Here, we aimed to elucidate the molecular mechanisms underlying the protective effects of chicoric acid in DSS-induced colitis. Mice with DSS-induced colitis (UC mice) were treated for a week with chicoric acid. Symptoms of colitis, colonic pathology, inflammation-related indicators, and intestinal mucosal barrier function were evaluated. RNA sequencing was performed on colon tissues to obtain differentially expressed genes. The deubiquitinating enzyme USP9X was selected, and the inhibitory and targeting effects of chicoric acid on USP9X were subsequently determined. In vivo and in vitro, DSS-induced colitis was treated with USP9X inhibitors WP1130 and EOAI3402143. Ubiquitination label-free quantitative proteomic analysis was performed to identify protein peptides that may undergo de-ubiquitination by USP9X. Co-immunoprecipitation (Co-IP), immunohistochemistry and western blotting were used to validate in vivo and in vitro results. Chicoric acid significantly alleviated clinical activity and histological changes, inhibited pro-inflammatory cytokine production and improved integrity of the intestinal barrier in UC mice. Moreover, chicoric acid suppressed USP9X expression in colonic tissues from UC mice. Furthermore, USP9X contributed to promoting the onset of UC and that insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) was deubiquitinated by USP9X. Chicoric acid ameliorated DSS-induced colitis by targeting the USP9X/IGF2BP2 axis, indicating that targeting the USP9X/IGF2BP2 axis presents a promising and innovative therapeutic approach for the treatment of UC.

Single-atom nanozyme liposome-integrated microneedles for in situ drug delivery and anti-inflammatory therapy in Parkinson’s disease

Treatment for Parkinson’s disease (PD) has been impeded by inefficient treatment results and multiple membrane barriers during drug delivery. This study reports the design, synthesis, and application of microneedles (MNs) loaded with mitochondrion-targeted liposome encapsulated iron (Fe)-isolated single-atom nanozymes (Mito@Fe-ISAzyme, MFeI), called MFeI MNs, for in situ drug delivery into the brain parenchyma and efficient enrichment of drugs in lesion sites. In in vitro experiments, MFeI can scavenge reactive oxygen species (ROS) and protect the neurons via mitochondrial targeting, guaranteeing the subsequent treatment of PD. Using PD mouse models, we compared the intravenous injection of MFeI with the brain in situ administration of MFeI MNs (in situ MFeI MNs). Results showed that in situ MFeI MNs significantly improved the deep penetration of the drug into brain parenchyma, especially in the vital pathological sites such as the substantia nigra pars compacta and striatum. Importantly, ROS elimination and neuroinflammatory remission in the lesion site were observed, thereby efficiently alleviating the behavioral disorders and pathological symptoms of PD mice. Therefore, the MNs system for in situ single-atom nanozyme liposome delivery exhibits great potential in PD treatment.Graphical abstract

Diffuse meningeal melanocytosis – a silent culprit

Abstract Introduction/Objective Diffuse meningeal melanocytosis is a rare melanocytic proliferation that poses significant risk of severe hydrocephalus and mortality among children and young adults. Although the clonal melanocytes do not typically exhibit malignant morphological features, their capability for extensive invasion and malignant-like behavior necessitates tissue biopsy alongside immunohistochemical and molecular testing for definitive diagnosis. Methods/Case Report A 17-year-old male presented with progressive headaches, photophobia, and nausea, initially attributed to migraines. Neuro-opthalmological assessment revealed papilledema, leading to a diagnosis of idiopathic intracranial hypertension. Serial imaging showed fluctuating leptomeningeal enhancement and moderate communicating hydrocephalus without parenchymal lesions. Therapeutic lumbar punctures provided modest symptom improvement; increased opening pressure was observed. Evaluation of seven CSF specimens showed low glucose levels, increased cellularity consisting of bland appearing epithelioid cells of unknown etiology, and increased lymphocytes. Infectious causes were excluded. Due to the indeterminate CSF findings, discussion between the cytopathologist and neuro-opthamologist was crucial to facilitate tissue biopsy to exclude a neoplastic process. Subsequent shunt placement and cerebral cortex biopsy revealed neoplastic cells with sheet-like architecture coating the dura without overt brain invasion. The tumor cells had eosinophilic cytoplasm without pigment and enlarged nuclei with irregular contours, vesicular chromatin, and prominent nucleoli. No high-grade features were seen. Immunohistochemical stains were positive for MART1, HMB45, and PRAME, consistent with a melanocytic lesion. FISH melanoma panel was negative. The final diagnosis was diffuse meningeal melanocytic neoplasm, most consistent with meningeal melanocytosis. The patient received chemotherapy with improved symptoms and stable disease. Results (if a Case Study enter NA) NA Conclusion Diffuse meningeal melanocytosis is a challenging cytologic diagnosis as melanocytes can morphologically mimic lymphocytes and monocytes, and the low cellularity of CSF specimens often results in insufficient cell blocks for ancillary tests. The direct communication of the pathologist with the clinical team to correlate pathology, radiology, and clinical symptoms was essential to ensure the proper management of this patient.

Identification and characteristics of Plesiomonas shigelloides isolated from Mastacembelus armatus

Plesiomonas shigelloides (P. shigelloides), a dominant pathogenic strain identified as YY001, was successfully isolated and characterized from the hepatopancreas of diseased Mastacembelus armatus (M. armatus) for the first time. The strain was identified through a comprehensive approach that included morphological, physiological, and biochemical characterization, as well as 16S rRNA, 23S rRNA, and gyrB gene sequence analysis. Strain YY001 is classified as a Gram-negative bacterium, with optimal growth conditions observed at 28°C and pH 7.0. Results from the bacterium hemolysis test indicated the absence of hemolytic activity in YY001. However, the strain exhibited amplification of nine virulence genes: nanE, waaA, clpP, ssb, actP, aphA, astA, astD, and astB. Drug-resistance testing showed that YY001 displayed resistance only to penicillin G, oxacillin, norfloxacin, and tetracycline, while remaining sensitive to the majority of other antibiotics. Furthermore, nine drug-resistance genes, including emrD, catB, macB, ksgA, tolC, bacA, MdfA, sul1, and DegP, were detected through amplification. Experimental infection demonstrated that YY001 induced symptoms such as abdominal swelling, visceral edema, and hemorrhage, with hepatopancreatic manifestations being particularly severe. The median lethal dosage of strain YY001 in M. armatus was 9.7×108 colony-forming units (CFU)/mL within 48 h, and 4.9×106 CFU/mL within 192 h under the conditions of intraperitoneal injection. The hepatopancreas, gill, and intestine of infected fish showed obvious pathological symptoms, including tissue loosening, hemorrhage, and cell necrosis. The results of this study provided evidence for a more comprehensive understanding of P. shigelloides strain YY001 infection in M. armatus.

Optical Coherence Tomography and Optical Coherence Tomography Angiography in Optic Nerve Disorders

Optic nerve disorders encompass a wide range of diseases. While it may be an isolated disease, such as optic disc drusen, it may also occur as a symptom of pathology in the central nervous system, such as multiple sclerosis. Optical coherence tomography (OCT) is an important auxiliary test used in optic nerve disorders as it allows cross-sectional imaging of the retina and optic nerve head at high resolution. OCT is used in the diagnosis of optic nerve disorders, evaluation of response to treatment, and prediction of visual prognosis by measuring retinal layers such as the ganglion cell layer (GCL) and retinal nerve fiber layer (RNFL).

Toward an animal model of Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is a rare and fatal neurodegenerative tauopathy which, with a rapid clinical progression coupled to a strong degree of clinico-pathologic correlation, has been suggested to be a "frontrunner" in translational development for neurodegenerative proteinopathies. Elegant studies in animals have contributed greatly to our understanding of disease pathogenesis in PSP. However, presently no animal model replicates the key anatomical and cytopathologic hallmarks, the spatiotemporal spread of pathology, progressive neurodegeneration, or locomotor and cognitive symptoms that characterize PSP. Current models therefore likely fail to recapitulate the key mechanisms that underly the pathological progression of PSP, impeding their translational value. Here we review what we have learned about PSP from work in animals to date, examine the gaps in modeling the disease and discuss strategies for the development of refined animal models that will improve our understanding of disease pathogenesis and provide a critical platform for the testing of novel therapeutics for this devastating disease.

Loss of Control Eating in Adults With Impulsive and/or Inattentive Tendencies.

Previous research has tended to consider impulsive, inattentive, and loss of control eating (LOC) tendencies as symptoms of greater pathologies in treatment-seeking samples. However, inattentive and impulsive tendencies and LOC often co-occur. Although LOC is an important diagnostic component of disordered eating (ED), it has recently been argued to be a dysregulated eating behavior in its own right. The purpose of the current self-report study was, therefore, to investigate the association between impulsive and inattentive tendencies and LOC in adults after accounting for ED. A community sample of 516 adults was surveyed online about their inattentive and impulsive tendencies, LOC, and ED behaviors. A hierarchical multiple linear regression revealed ED, inattentive, and impulsive symptoms to be independent, significant, positive predictors of LOC. These findings suggest that the levels of inattentive and, to a lesser extent, impulsive tendencies are significantly associated with LOC in adults, even after ED is accounted for. Moreover, inattentive tendencies were found to be more significantly associated with LOC than impulsive tendencies. These are novel and important findings that can be used to inform both clinicians and individuals with inattentive and impulsive tendencies alike of this association. Considering the well-documented adverse health and wellbeing outcomes associated with LOC, future feasibility trials are needed aimed at treating this co-occurrence.

Drug-resistant schizophrenia-like psychosis associated with temporal non-anaplastic pleomorphic xanthoastrocytoma: unusual revealing symptom of a rare pathology

Introduction and importance: Pleomorphic xanthoastrocytoma (PXA) was first described by Kepes et al. in 1979. Fewer than 200 cases have been reported in the literature. It generally involves the temporoparietal lobe. PXA has a favorable prognosis. The most reported clinical manifestation is epileptic seizures. Revealing psychiatric symptoms have an incidence varying from 50 to 78%. The most common symptoms encountered are anxiety disorders, depression, schizophrenia-like psychosis, cognitive dysfunction or even anorexia nervosa. Case presentation: Here, the authors report a new case of non-anaplastic pleomorphic xanthoastrocytoma revealed by a drug-resistant schizophrenia-like psychosis in a 26-year-old male patient known with epileptic seizures in whom these two pathologies were intertwined and had been evolving for 5 years. The postoperative course was uneventful, and positive symptoms of schizophrenia were relatively stabilized at discharge. Clinical discussion: Given the superficial hemispheric location of PXA, the most common clinical presentation is seizures. Psychiatric symptoms revealing brain tumors have an incidence varying from 50 to 78%. Most of these symptoms concern frontal and limbal tumors. In their case, the tumor was located in the right temporal lobe. Surgery was performed and postoperative course was uneventful even though there are conflicting reports regarding the importance of the surgical excision quality. Conclusion: PXA remains a rare and benign primary CNS tumor. Psychiatric disorders represent a rare revealing mode of this pathology, which must lead to neuroimaging in any patient carrying this type of symptoms.

Contribution of Pseudomonas aeruginosa − mediated club cell necroptosis to the bias of type 17 inflammation and steroid insensitivity in asthma

IntroductionOpportunistic pathogen infection is one of the important inducements for asthma exacerbation. Pseudomonas aeruginosa (PA) is a kind of dominant pathogenic bacteria in the respiratory tract that is associated with severe asthma, but the underlying mechanisms still remains unclear. ObjectivesTo examine the role of PA infection in the bias of the inflammatory endotype in asthma and its effect on the sensitivity to steroid therapy. MethodsAn adjusted HDM (House Dust Mite) −induced asthma model with PA inoculation in the airway was utilized to mimic the process of opportunistic PA infection in asthma, focusing on the interaction between bacteria and epithelium. Dexamethasone administration in vivo was used to test the sensitivity to steroid therapy. ResultsIt was uncovered that PA could promote the loss of club cells in the necroptosis pattern through cellular CYP450 activation, leading to an imbalance of inflammatory response and steroid insensitivity. Club cell loss results in the activation of cellular E-cadherin/β-catenin axis in the rest of club cells for goblet metaplasia and mucus hypersecretion, as well as epithelial damage and GR downregulation for steroid resistance. For clinical applications, the necroptosis inhibitor Nec-1 can effectively relieve the pathological symptoms of asthma in vivo. Meanwhile, CCSP administration in the airway can regulate the pulmonary inflammation and restore the steroid sensitivity in asthma. ConclusionThese experiments provide a novel mechanism of concurrent PA infection in asthma through club cell necroptosis and the pathological consequences. Nec-1 treatment and CCSP supplementation may be possible therapeutic strategies for asthma treatment.

Identification of NET formation and the renoprotective effect of degraded NETs in lupus nephritis.

To explore molecular biomarkers associated with the pathophysiology and therapy of lupus nephritis (LN), we conducted a joint analysis of transcriptomic data from 40 peripheral blood mononuclear cells (PBMCs) (GSE81622) and 21 kidney samples (GSE112943) from the Gene Expression Omnibus database using bioinformatics. A total of 976 and 2,427 differentially expressed genes (DEGs) were identified in PBMCs and renal tissues. Seven and two functional modules closely related to LN were identified. Further enrichment analysis revealed that the neutrophil activation pathway was highly active in both PBMCs and the kidney. Subsequently, 16 core genes closely associated with LN were verified by protein-protein interaction screening and quantitative PCR. In vitro cell models and MRL/lpr mouse models confirmed that the abnormal expression of these core genes was closely linked to neutrophil extracellular traps (NETs) generated by neutrophil activation, while degradation of NETs led to downregulation of core gene expression, thereby improving pathological symptoms of LN. Therefore, identification of patients with systemic lupus erythematosus exhibiting abnormal expression patterns for these core genes may serve as a useful indicator for kidney involvement. In addition, targeting neutrophils to modulate their activation levels and inhibit aberrant expression of these genes represents a potential therapeutic strategy for treating LN. NEW & NOTEWORTHY The mechanisms by which immune cells cause kidney injury in lupus nephritis are poorly understood. We integrated and analyzed the transcriptomic features of PBMCs and renal tissues from the GEO database to identify key molecular markers associated with neutrophil activation. We confirmed that neutrophil extracellular traps (NETs) formed by neutrophil activation promoted the upregulation of key genes in cell and animal models. Targeted degradation of NETs significantly ameliorated kidney injury in MRL/lpr mice.