A causal effects of gut microbiota in the development of migraine

Background: The causal association between the gut microbiome and the development of migraine and its subtypes remains unclear. Methods: The single nucleotide polymorphisms concerning gut microbiome were retrieved from the gene-wide association study (GWAS) of the MiBioGen consortium. The summary statistics datasets of migraine, migraine with aura (MA), and migraine without aura (MO) were obtained from the GWAS meta-analysis of the International Headache Genetics Consortium (IHGC) and FinnGen consortium. Inverse variance weighting (IVW) was used as the primary method, complemented by sensitivity analyses for pleiotropy and increasing robustness. Results: In IHGC datasets, ten, five, and nine bacterial taxa were found to have a causal association with migraine, MA, and MO, respectively, (IVW, all P < 0.05). Genus.Coprococcus3 and genus.Anaerotruncus were validated in FinnGen datasets. Nine, twelve, and seven bacterial entities were identified for migraine, MA, and MO, respectively. The causal association still exists in family.Bifidobacteriaceae and order.Bifidobacteriales for migraine and MO after FDR correction. The heterogeneity and pleiotropy analyses confirmed the robustness of IVW results. Conclusion: Our study demonstrates that gut microbiomes may exert causal effects on migraine, MA, and MO. We provide novel evidence for the dysfunction of the gut-brain axis on migraine. Future study is required to verify the relationship between gut microbiome and the risk of migraine and its subtypes and illustrate the underlying mechanism between them

Role of Eryptosis in Hemorrhagic Stroke

Erythrocytes undergo certain morphological changes resembling apoptosis during senescence or in an abnormal state/site, which is termed eryptosis. This process is characterized by phosphatidylserine (PS) exposure, membrane blebbing, and cell shrinkage. Eryptotic erythrocytes are subsequently removed via macrophage-mediated efferocytosis. In hemorrhagic stroke (HS), blood within an artery rapidly bleeds into the brain tissue or the subarachnoid space, resulting in severe neurological deficits. A hypoxic, over-oxidative, and pro-inflammatory microenvironment in the hematoma leads to oxidative stress, hyperosmotic shock, energy depletion, and Cl– removal in erythrocytes, which eventually triggers eryptosis. In addition, eryptosis following intracerebral hemorrhage favors hematoma clearance, which sheds light on a common mechanism of intrinsic phagocytosis. In this review, we summarized the canonical mechanisms of eryptosis and discussed its pathological conditions associated with HS. Understanding the role of eryptosis in HS may uncover additional potential interventions for further translational clinical research

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Potential causal association between gut microbiome and posttraumatic stress disorder

Funding Information: We thank the participants and working staff including the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group, the FinnGen consortium, and the MiBioGen consortium. Publisher Copyright: © 2024, The Author(s).Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms.publishersversionpublishe

Potential causal association between gut microbiome and posttraumatic stress disorder

Background: The causal effects of gut microbiome and the development of posttraumatic stress disorder (PTSD) are still unknown. This study aimed to clarify their potential causal association using mendelian randomization (MR). Methods: The summary-level statistics for gut microbiome were retrieved from a genome-wide association study (GWAS) of the MiBioGen consortium. As to PTSD, the Freeze 2 datasets were originated from the Psychiatric Genomics Consortium Posttraumatic Stress Disorder Working Group (PGC-PTSD), and the replicated datasets were obtained from FinnGen consortium. Single nucleotide polymorphisms meeting MR assumptions were selected as instrumental variables. The inverse variance weighting (IVW) method was employed as the main approach, supplemented by sensitivity analyses to evaluate potential pleiotropy and heterogeneity and ensure the robustness of the MR results. We also performed reverse MR analyses to explore PTSD’s causal effects on the relative abundances of specific features of the gut microbiome. Results: In Freeze 2 datasets from PGC-PTSD, eight bacterial traits revealed a potential causal association between gut microbiome and PTSD (IVW, all P < 0.05). In addition, Genus.Dorea and genus.Sellimonas were replicated in FinnGen datasets, in which eight bacterial traits revealed a potential causal association between gut microbiome and the occurrence of PTSD. The heterogeneity and pleiotropy analyses further supported the robustness of the IVW findings, providing additional evidence for their reliability. Conclusion: Our study provides the potential causal impact of gut microbiomes on the development of PTSD, shedding new light on the understanding of the dysfunctional gut-brain axis in this disorder. Our findings present novel evidence and call for investigations to confirm the association between their links, as well as to illuminate the underlying mechanisms

Identification of RPL5 and RPL10 as novel diagnostic biomarkers of Atypical teratoid/rhabdoid tumors

Abstract Background Rhabdoid tumors (RTs) are aggressive tumors that occur most frequently in children under 2 years old, which often invade kidney (KRTs) and Center Nervous System, named Atypical teratoid/rhabdoid tumors (AT/RTs). RTs often progress fast and lead to a high lethality. RTs have a low incidence, we can hardly accumulate enough samples to elicit the diagnosis. More importantly, histologically, RTs present a host of neural, epithelial, mesenchymal, or ependymal patterns, which makes them rather variable and difficult to diagnose. Molecularly, RTs are diagnosed mainly on the lack of SMARCB1/INI1 protein expression, which, on the one hand, accounts for 75% of RTs, on the other hand, loss of expression of SMARCB1 is not exclusive to RTs. So, there is a need to find more accurate diagnose markers of RTs. Methods In this study, we analyzed 109 samples including AT/RT, KRT and corresponding normal samples downloaded form NCBI GEO database. First, we identified the differentially expressed lncRNAs and PCGs in AT/RT, KRT and corresponding normal samples. Second, we evaluated the co-expression relationship between lncRNA and PCG, and defined four types of the dysregulated PCG-lncRNA pairs. Third, we compared the differentially expressed genes, the dysregulated PCG-lncRNA pairs and commonly known cancer genes, we get potential diagnostic markers. Then, the potential diagnostic markers were subjected to Receiver operating characteristic (ROC) analysis to assess the diagnostic accuracy. Importantly, differential expression of the marker genes in different tumors was shown to distinguish AT/RT and KRT from other pediatric tumors specifically. Results We compared the expression profiles between 47 AT/RTs, 31 KRTs, 8 normal brain samples, and 23 normal kidney samples. After applying a stringent set of criteria on the gene expression profiles, we identified 3667 PCGs and 81 lncRNAs differentially expressed in AT/RT, 3809 PCGs and 34 lncRNAs differentially expressed in KRT tissues. Next, we compared the three sets(AT/RT versus control brain samples, KRT versus control kidney samples, and AT/RT versus KRT) of differentially expressed lncRNAs and PCGs, 491 PCGs and 2 lncRNAs appeared in all three sets. We examined the correlation of the expression levels of these genes in the ‘three-set overlap’ group and identified four types of dysregulated lncRNAs and PCGs. By compared these genes to the well-known cancer driver genes, 19 PCGs were selected as potential candidates of diagnostic markers. Filtered with the number of the corresponding co-expressed lncRNA (namely “degree”), eight PCGs with more than five lncRNAs in the ‘three-set overlap’ group were selected as candidate diagnostic markers. Among them, RPL5 and RPL10 exhibited high sensitivity and specificity in diagnosis of AT/RT and KRT. However, when these two genes were used to distinguish AT/RT and KRT from other pediatric tumors, only AT/RT can be distinguished from medulloblastoma. Conclusions Our study mined existing GEO datasets for novel diagnostic markers associated with Rhabdoid tumors, and identified RPL5 and RPL10 as potential diagnostic markers for AT/RT. These two biomarkers may be used as supplementary biomarkers to canonical diagnostic tools such as biopsy and immunohistochemistry

White Matter Injury after Intracerebral Hemorrhage: Pathophysiology and Therapeutic Strategies

Intracerebral hemorrhage (ICH) accounts for 10%–30% of all types of stroke. Bleeding within the brain parenchyma causes gray matter (GM) destruction as well as proximal or distal white matter (WM) injury (WMI) due to complex pathophysiological mechanisms. Because WM has a distinct cellular architecture, blood supply pattern and corresponding function, and its response to stroke may vary from that of GM, a better understanding of the characteristics of WMI following ICH is essential and may shed new light on treatment options. Current evidence using histological, radiological and chemical biomarkers clearly confirms the spatio-temporal distribution of WMI post- ICH. Although certain types of pathological damage such as inflammatory, oxidative and neuro-excitotoxic injury to WM have been identified, the exact molecular mechanisms remain unclear. In this review article, we briefly describe the constitution and physiological function of brain WM, summarize evidence regarding WMI, and focus on the underlying pathophysiological mechanisms and therapeutic strategies

Predictors of Acute Vertebrobasilar Vasospasm following Tumor Resection in the Foramen Magnum Region.

Cerebral vasospasm can occur after skull base tumor removal. Few studies concentrated on the posterior circulation vasospasm after tumor resection in the posterior fossa. We aimed to identify the risk factors associated with postoperative vertebrobasilar vasospasm after tumor resection in the foramen magnum.We retrospectively reviewed the data of 62 patients with tumors in the foramen magnum at our institution from January 2010 to January 2015. The demographic data, tumor features, surgical characteristics were collected. Vertebrobasilar vasospasm was evaluated by bedside transcranial Doppler before surgery and on postoperative day 1, 3, 7. Univariate and multivariate analyses were performed to determine the predictors of postoperative vasospasm in the posterior circulation.Vertebrobasilar vasospasm was detected in 28 (53.8%) of the 62 patients at a mean time of 3.5 days after surgery. There were 5 (8%) patients with severe vasospasm according to the grading criteria. Age, tumor type, tumor size, vertebral artery encasement, and surgical time were significantly related to vasospasm in the univariate analysis. Further multivariate analysis demonstrated that only age and vertebral artery encasement were independent risk factors predicting the occurrence of postoperative vertebrobasilar vasospasm.The incidence of acute vertebrobasilar vasospasm is not uncommon after foramen magnum tumor resection. Age and vertebral artery encasement are significantly correlated with postoperative vasospasm. Close monitoring of vasospasm should be given to patients with younger age and the presence of vertebral artery encasement on the preoperative imaging to facilitate early diagnosis and intervention

Effect of corticosteroids in patients with COVID-19: a Bayesian network meta-analysis

Objectives: We sought to perform a network meta-analysis to compare the safety and efficacy of the systemic administration of corticosteroids for the treatment of COVID-19. Methods: A Bayesian network meta-analysis was performed to combine the direct and indirect evidence. The surface under the cumulative ranking curve was obtained to estimate the ranking probability of the treatment agents for each outcome. The efficacy outcome was 28-day all-cause mortality. The safety outcome was serious adverse events. Results: A total of 16 trials with 2992 patients comparing four treatments (dexamethasone, hydrocortisone, methylprednisolone, and placebo) were identified. Direct analysis showed that corticosteroids were associated with a reduced risk of 28-day mortality compared with usual care (risk ratio [RR] 0.83; 95% confidence interval [CrI] 0.70-0.99). Network analysis showed that the pooled RR was 0.63 (95% CrI 0.39-0.93) for all-cause mortality at 28 days comparing methylprednisolone with usual care or placebo (surface under the cumulative ranking curve: 91%). Our analysis demonstrated that patients who received a low dose of corticosteroids (RR 0.80; 95% CrI 0.70-0.91) and a long course of treatment (RR 0.81; 95% CrI 0.71-0.91) had higher survival rates than patients in the placebo group. Conclusion: Administration of corticosteroids was associated with a reduced all-cause mortality at 28 days compared with placebo or usual care. Our analysis also confirmed the mortality benefit associated with low-dose and long-term treatment with corticosteroids