Phase 1 study of safety and preliminary efficacy of intranasal transplantation of human neural stem cells (ANGE-S003) in Parkinson's disease.

BACKGROUND: Intranasal transplantation of ANGE-S003 human neural stem cells showed therapeutic effects and were safe in preclinical models of Parkinson's disease (PD). We investigated the safety and tolerability of this treatment in patients with PD and whether these effects would be apparent in a clinical trial. METHODS: This was a 12-month, single-centre, open-label, dose-escalation phase 1 study of 18 patients with advanced PD assigned to four-time intranasal transplantation of 1 of 3 doses: 1.5 million, 5 million or 15 million of ANGE-S003 human neural stem cells to evaluate their safety and efficacy. RESULTS: 7 patients experienced a total of 14 adverse events in the 12 months of follow-up after treatment. There were no serious adverse events related to ANGE-S003. Safety testing disclosed no safety concerns. Brain MRI revealed no mass formation. In 16 patients who had 12-month Movement Disorder Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) data, significant improvement of MDS-UPDRS total score was observed at all time points (p<0.001), starting with month 3 and sustained till month 12. The most substantial improvement was seen at month 6 with a mean reduction of 19.9 points (95% CI, 9.6 to 30.3; p<0.001). There was no association between improvement in clinical outcome measures and cell dose levels. CONCLUSIONS: Treatment with ANGE-S003 is feasible, generally safe and well tolerated, associated with functional improvement in clinical outcomes with peak efficacy achieved at month 6. Intranasal transplantation of neural stem cells represents a new avenue for the treatment of PD, and a larger, longer-term, randomised, controlled phase 2 trial is warranted for further investigation.

Using circulating microbial cell-free DNA to identify persistent Treponema pallidum infection in serofast syphilis patients.

The question of whether serofast status of syphilis patients indicates an ongoing low-grade Treponema pallidum (T. pallidum) infection remains unanswered. To address this, we developed a machine learning model to identify T. pallidum in cell-free DNA (cfDNA) using next-generation sequencing (NGS). Our findings showed that a TP_rate cut-off of 0.033 demonstrated superior diagnostic performance for syphilis, with a specificity of 92.3% and a sensitivity of 71.4% (AUROC = 0.92). This diagnosis model predicted that 20 out of 92 serofast patients had a persistent low-level infection. Based on these predictions, re-treatment was administered to these patients and its efficacy was evaluated. The results showed a statistically significant decrease in RPR titers in the prediction-positive group compared to the prediction-negative group after re-treatment (p < 0.05). These findings provide evidence for the existence of T. pallidum under serofast status and support the use of intensive treatment for serofast patients at higher risk in clinical practice.

Large-Scale Proteome Profiling Identifies Biomarkers Associated with Suspected Neurosyphilis Diagnosis.

Neurosyphilis (NS) is a central nervous system (CNS) infection caused by Treponema pallidum (T. pallidum). NS can occur at any stage of syphilis and manifests as a broad spectrum of clinical symptoms. Often referred to as "the great imitator," NS can be easily overlooked or misdiagnosed due to the absence of standard diagnostic tests, potentially leading to severe and irreversible organ dysfunction. In this study, proteomic and machine learning model techniques are used to characterize 223 cerebrospinal fluid (CSF) samples to identify diagnostic markers of NS and provide insights into the underlying mechanisms of the associated inflammatory responses. Three biomarkers (SEMA7A, SERPINA3, and ITIH4) are validated as contributors to NS diagnosis through multicenter verification of an additional 115 CSF samples. We anticipate that the identified biomarkers will become effective tools for assisting in diagnosis of NS. Our insights into NS pathogenesis in brain tissue may inform therapeutic strategies and drug discoveries for NS patients.

Explaining differences in autism detection timing: Age of diagnosis and associated individual and socio-familial factors in Chinese children.

LAY ABSTRACT: Timely detection is an issue of paramount importance in the care of children with autism spectrum disorder. Whether the delayed autism spectrum disorder diagnosis can be explained by children's clinical presentations and socio-familial status in China is a question to be addressed. We investigated 1235 autism spectrum disorder children from 132 rehabilitation organisations in Shenzhen, China. These children were found to have a mean age of diagnosis of 31.4 ± 12.7 months and a median age of diagnosis of 30.0 months. The majority of these children were able to receive their diagnosis during toddlerhood. However, about one in six were not diagnosed until they entered preschool or later, thus missing the golden window of opportunity for early intervention. The age of diagnosis was likely to be late if the children were older, were less severe and presented with no intellectual impairment. The odds of having a delayed autism spectrum disorder diagnosis were more than 9 times higher among migrant autism spectrum disorder children than among those with local household registrations, thus underscoring the importance of identifying culturally sensitive socio-economic determinants in autism spectrum disorder detection, as these factors are likely to affect the quality of life of many autism spectrum disorder children and their families.

Analysing the causal relationship between potentially protective and risk factors and cutaneous melanoma: A Mendelian randomization study.

BACKGROUND: Previous observational studies reported altered melanoma risks in relation to many potential factors, such as coffee intake, smoking habits and photodamage-related conditions. Considering the susceptibility of epidemiological studies to residual confounders, there remains uncertainty about the actual causal roles of these reported factors in melanoma aetiology. OBJECTIVES: This study aims to investigate the causal association between cutaneous melanoma (CM) and previously reported factors: coffee intake, alcohol consumption, lifetime smoking, socioeconomic status (SES), ease of skin tanning, childhood sunburn and facial ageing, providing insight into its underlying aetiology and preventative strategies. METHODS: We utilized a two-sample MR analysis on data from the largest meta-analysis summary statistics of confirmed cutaneous melanoma including 30,134 patients. Genetic instrumental variables were constructed by identifying single nucleotide polymorphisms (SNPs) that associate with corresponding factors. Inverse variance weighted (IVW) was the primary MR method. For sensitivity and heterogeneity, MR Egger, weighted median, simple mode, weighted mode and MR Egger intercept tests were examined. RESULTS: Cutaneous melanoma risks were found to be elevated in association with a predisposition towards ease of skin tanning (IVW: OR = 2.842, 95% CI 2.468-3.274, p < 0.001) and with childhood sunburn history (IVW: OR = 6.317, 95% CI 4.479-8.909, p < 0.001). Repeated MR after removing potential confounders and outliers demonstrated resolved horizontal pleiotropy and statistically significant results that closely mirrored the initial findings. Other potential factors, such as coffee intake, alcohol consumption, smoking and socioeconomic status (SES), indicated insignificant effects on melanoma risk in the analysis, and therefore, our Mendelian randomization study does not support their roles in modifying melanoma risks. CONCLUSIONS: Our extensive MR analysis provides strong evidence of the causative role of ease of skin tanning and childhood sunburn history in elevating melanoma risk. Curtailing ultraviolet radiation (UVR) exposure may be the single best preventative strategy to reduce melanoma risk.

Phenolic acids from Prunella vulgaris alleviate cardiac remodeling following myocardial infarction partially by suppressing NLRP3 activation.

Acute myocardial infarction (MI) is one of the leading causes of mortality around the world. Prunella vulgaris (Xia-Ku-Cao in Chinese) is used in traditional Chinese medicine practice for the treatment of cardiovascular diseases. However, its active ingredients and mechanisms of action on cardiac remodeling following MI remain unknown. In this study, we investigated the cardioprotective effect of P. vulgaris on MI rat models. MI rats were treated with aqueous extract of P. vulgaris or phenolic acids from P. vulgaris, including caffeic acid, ursolic acid or rosmarinic acid, 1 day after surgery and continued for the following 28 days. Then the cardioprotective effect, such as cardiac function, inflammatory status, and fibrosis areas were evaluated. RNA-sequencing (RNA-seq) analysis, real-time polymerase chain reaction (PCR), western blotting, and ELISA were used to explore the underlying mechanism. In addition, ultra-high performance liquid chromatography/mass spectrometer analysis was used to identify the chemicals from P. vulgaris. THP-1NLRP3-GFP cells were used to confirm the inhibitory effect of P. vulgaris and phenolic acids on the expression and activity of NLRP3. We found that P. vulgaris significantly improved cardiac function and reduced infarct size. Meanwhile, P. vulgaris protected cardiomyocyte against apoptosis, evidenced by increasing the expression of anti-apoptosis protein Bcl-2 in the heart and decreasing lactate dehydrogenase (LDH) levels in serum. Results from RNA-seq revealed that the therapeutic effect of P. vulgaris might relate to NLRP3-mediated inflammatory response. Results from real-time PCR and western blotting confirmed that P. vulgaris suppressed NLRP3 expression in MI heart. We also found that P. vulgaris suppressed NLRP3 expression and the secretion of HMGB1, IL-1ß, and IL-18 in THP-1NLRP3-GFP cells. Further studies indicated that the active components of P. vulgaris were three phenolic acids, those were caffeic acid, ursolic acid, and rosmarinic acid. These phenolic acids inhibited LPS-induced NLRP3 expression and activity in THP-1 cells, and improved cardiac function, suppressed inflammatory aggregation and fibrosis in MI rat models. In conclusion, our study demonstrated that P. vulgaris and phenolic acids from P. vulgaris, including caffeic acid, ursolic acid, and rosmarinic acid, could improve cardiac function and protect cardiomyocytes from ischemia injury during MI. The mechanism was partially related to inhibiting NLRP3 activation.

SARS-CoV-2-infected hiPSC-derived cardiomyocytes reveal dynamic changes in the COVID-19 hearts.

BACKGROUND: The ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease's extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients. METHODS: In this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection. RESULTS: To this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern. CONCLUSIONS: Our findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease.

Clinical and Laboratory Characteristics, Neuroimaging Alternations and Treatment Response of 25 HIV-Negative General Paresis Patients.

Purpose: General paresis is a common type of neurosyphilis featuring progressive cognitive deterioration. The lack of a golden standard of diagnosis and its nonspecific clinical manifestations resulted in a high rate of misdiagnoses. This study aims to investigate the clinical, laboratory and radiological presentations of general paresis and enrich its knowledge for timely diagnoses. Patients and methods: The study collected hospitalized patients admitted for general paresis from September 2002 to November 2022. Their socio-demographical and medical status, clinical presentations, cognitive assessments, laboratory and radiographical manifestations and treatment information were collected retrospectively. Results: A total of 20 males and 5 females were included. Patients' ages ranged from 30 to 66 years (average 50.3 years). The average and median time for diagnosing general paresis was 14.1 months and 10.0 months respectively. The most frequent initial symptom is memory deterioration (68.0%). Impaired calculative ability and memory deterioration were the most frequent cognitive anomalies, as found in 50% and 45.4% of subjects during examination. The mean and median scores of MoCA was 16.7 and 17 respectively. Serological tests revealed positive TPPA for all patients and a median RPR titer at 1:64 positive. All CSF samples with TPPA and FTA-ABS results reported positivity. The MRI manifestations of general paresis include patchy or speckled hyperintensities (70.8%) and cerebral atrophy (45.8%). The most common lesioned sites in MRI were the ventricular and paraventricular area (50.0%) and temporal lobes (45.8%). For treatment, penicillin-based anti-syphilitic plans were adopted in 17 patients (68.0%). Conclusion: The clinical features and radiological alternations of general paresis patients often exhibited diverse and nonspecific alternations. However, some specific clinical manifestations and auxiliary examinations can provide meaningful clues for the identification and differential diagnosis of this disease.

Injury mechanism of COVID-19-induced cardiac complications.

Heart dysfunction is one of the most life-threatening organ dysfunctions caused by coronavirus disease 2019 (COVID-19). Myocardial or cardiovascular damage is the most common extrapulmonary organ complication in critically ill patients. Understanding the pathogenesis and pathological characteristics of myocardial and vascular injury is important for improving clinical diagnosis and treatment approach. Herein, the mechanism of direct damage caused by severe acute respiratory syndrome coronavirus 2 to the heart and secondary damage caused by virus-driven inflammation was reviewed. The pathological mechanism of ischemia and hypoxia due to microthrombosis and inflammatory injury as well as the injury mechanism of tissue inflammation and single myocardial cell necrosis triggered by the viral infection of pericytes or macrophages, hypoxia, and energy metabolism disorders were described. The latter can provide a novel diagnosis, treatment, and investigation strategy for heart dysfunctions caused by COVID-19 or the Omicron variant.

Assessing the quality of care for skin malignant melanoma on a global, regional, and national scale: a systematic analysis of the global burden of disease study from 1990 to 2019.

Malignant melanoma (MM) is a highly aggressive form of skin cancer with increasing global incidence rates, particularly in developed countries. Variations in the prevalence and quality of care provided to patients with melanoma exist across different regions and across different sex and age. Assessing the global burden of melanoma and evaluating the quality of care can provide valuable insights for developing targeted interventions in certain underperforming regions and improving patient outcomes. This study aimed to systematically analyze the Global Burden of Disease Study from 1990 to 2019 to assess the quality of care for skin malignant melanoma on a global scale. We conducted a comprehensive literature review and extracted data on melanoma incidence, mortality, and disability-adjusted life years (DALYs) from the Global Burden of Disease Study. We incorporated these variables using principal component analysis (PCA) to form an informative single variable of quality of care index (QCI) and analyzed its spatial-temporal variations as well as disparities across age, sex and socio-demographic index (SDI). The overall Quality of Care Index (QCI) for melanoma improved from 82.81 in 1990 to 91.29 in 2019. The QCI score showed a positive correlation with socioeconomic status across regions. Australia ranked highest in QCI (99.96), while Central African Republic, and Kiribati had the lowest scores. China and Saudi Arabia showed significant QCI improvement, while the QCI of the Democratic People's Republic of Korea, Zimbabwe, and Guam decreased from 1990 to 2019. The highest QCI scores were observed in the age groups of 20-39 years old (93.40-94.65). Gender disparities narrowed globally in these three decades, but lower Socio-demographic Index (SDI) regions showed increased gender inequities. Our findings highlighted the spatial-temporal variations in the quality of care of MM as well as its disparities across different SDI levels, age groups and sex. These findings offer valuable insights and guidance for implementing focused interventions and resource allocation to enhance the quality of care and overall outcomes for MM worldwide, especially for underperforming regions.

A Neglected Narrative in the COVID-19 Pandemic: Epidemiological and Clinical Impacts of the COVID-19 Outbreak on Syphilis.

The COVID-19 pandemic has profoundly changed our lives. While healthcare resources were redistributed and mobilized to focus on dealing with the COVID-19 crisis, there have been unmet medical needs of patients with other diseases such as syphilis, weaving an integral but neglected component of the pandemic story. In different countries, the epidemiology of newly reported syphilis underwent diverse changes during the COVID-19 pandemic. Asymptomatic cases experienced the largest decline in number. From the perspective of transmission, on one hand, the implementation of lockdown measures led to a higher degree of abstinence and sex distancing in many countries, thereby reducing the transmission of syphilis. On the other hand, vertical transmission was reported to have increased significantly during COVID-19. Meanwhile, the volume of STI clinic capacity declined, and STI staff were redeployed to facilitate the contact tracing of COVID-19. As a result, many STI centers converted traditional in-person clinical services to telemedicine and self-testing. However, syphilis testing and clinical treatment cannot fully adapt to this conversion. In syphilis diagnosis, COVID-19 infection and vaccination were reported to cause false positivity in syphilis serological tests. Diverse cutaneous manifestations of COVID-19 could resemble the skin lesions in syphilis patients, requiring differential diagnosis from clinicians. As for the post-pandemic years, consequent to service interruptions and diagnosis delays, a surge in the number of confirmed cases of syphilis is expected. The COVID-19 pandemic has also been a meaningful lesson for the control and prevention of infectious diseases. The experience in combating COVID-19 has underscored the importance of maintaining a robust and well-supported medical system for the provision of sexual health services and better healthcare equality even during eras of crisis, not least for syphilis patients.

Telomere length is associated with increased risk of cutaneous melanoma: a Mendelian randomization study.

RESULTS: The MR analysis using two TL GWAS datasets revealed strong and consistent evidence that long TL is causally associated with an increased risk of CM. The analysis of the Codd et al. dataset found that long TL significantly predicted an elevated risk of CM (IVW OR = 2.411, 95% CI 2.092-2.780, P = 8.05E-34). Similarly, the analysis of the Li et al. dataset yielded consistent positive results across all MR methods, providing further robustness to the causal relationship (IVW OR = 2.324, 95% CI 1.516-3.565, P = 1.11E-04). The study provides evidence for a causal association between TL and CM susceptibility, indicating that longer TL increases the risk of developing CM and providing insight into the unique telomere biology in melanoma pathogenesis. Telomere maintenance pathways may be a potential target for preventing and treating CM.

Antenatal mobile-delivered mindfulness-based intervention to reduce perinatal depression risk and improve obstetric and neonatal outcomes: A randomized controlled trial.

OBJECTIVES: One in five mothers will experience perinatal depression (PND) during pregnancy and within their first year following childbirth. Current evidence suggests the short-term efficacy of Mindfulness-based interventions (MBI) for perinatal women, but the extent to which this positive impact remains the early postpartum period is unclear. This study investigated the short- and maintenance efficacy of a mobile-delivered four-immeasurable MBI on PND, and obstetric and neonatal outcomes. METHODS: Seventy-five adult pregnant women suffering from heightened distress were randomized to receive a mobile-delivered four-immeasurable MBI (n = 38) or a web-based perinatal education program (n = 37). PND was measured by Edinburgh Postnatal Depression Scale at baseline, post-intervention, 37th-week gestation, and 4-6 weeks postpartum. Outcomes also included obstetric and neonatal outcomes, trait mindfulness, self-compassion, and positive affect. RESULTS: Participants reported an average age of 30.6 (SD = 3.1) years with a mean gestational age of 18.8 (SD = 4.6) weeks. In intention-to-treat analyses, women in the mindfulness group showed a significantly greater reduction in depression from baseline to post-intervention (adjusted mean change difference [ß] = -3.9; 95%CI = [-6.05, -1.81]; d = -0.6), and the reduction sustained until 4-6 weeks postpartum (ß = -6.3; 95%CI = [-8.43, -4.12]; d = -1.0), compared with control. They had a significantly reduced risk of emergent cesarean section (relative risk = 0.5) and gave birth to infants with higher Apgar scores (ß = 0.6;p = .03; d = 0.7). Depression reduction before giving birth significantly mediated the intervention effect on lowering the emergency cesarean risk. CONCLUSIONS: With a reasonably low dropout rate (13.2 %), the mobile-delivered MBI can be an acceptable and effective intervention for reducing depression throughout pregnancy and postpartum. Our study also suggests the potential benefits of early prevention for mitigating emergent cesarean section risk and enhancing neonatal health.

Suxiao Jiuxin Pill attenuates acute myocardial ischemia via regulation of coronary artery tone.

Suxiao Jiuxin Pill (SJP) is a well-known traditional Chinese medicine drug used to manage heart diseases. This study aimed at determining the pharmacological effects of SJP in acute myocardial infarction (AMI), and the molecular pathways its active compounds target to induce coronary artery vasorelaxation. Using the AMI rat model, SJP improved cardiac function and elevated ST segment. LC-MS and GC-MS detected twenty-eight non-volatile compounds and eleven volatile compounds in sera from SJP-treated rats. Network pharmacology analysis revealed eNOS and PTGS2 as the key drug targets. Indeed, SJP induced coronary artery relaxation via activation of the eNOS-NO pathway. Several of SJP's main compounds, like senkyunolide A, scopoletin, and borneol, caused concentration-dependent coronary artery relaxation. Senkyunolide A and scopoletin increased eNOS and Akt phosphorylation in human umbilical vein endothelial cells (HUVECs). Molecular docking and surface plasmon resonance (SPR) revealed an interaction between senkynolide A/scopoletin and Akt. Vasodilation caused by senkyunolide A and scopoletin was inhibited by uprosertib (Akt inhibitor) and eNOS/sGC/PKG axis inhibitors. This suggests that senkyunolide A and scopoletin relax coronary arteries through the Akt-eNOS-NO pathway. In addition, borneol induced endothelium-independent vasorelaxation of the coronary artery. The Kv channel inhibitor 4-AP, KCa2+ inhibitor TEA, and Kir inhibitor BaCl2 significantly inhibited the vasorelaxant effect of borneol in the coronary artery. In conclusion, the results show that Suxiao Jiuxin Pill protects the heart against acute myocardial infarction.

Insights into the Occurrence, Fate, Impacts, and Control of Food Additives in Food Waste Anaerobic Digestion: A Review.

The recovery of biomass energy from food waste through anaerobic digestion as an alternative to fossil energy is of great significance for the development of environmental sustainability and the circular economy. However, a substantial number of food additives (e.g., salt, allicin, capsaicin, allyl isothiocyanate, monosodium glutamate, and nonnutritive sweeteners) are present in food waste, and their interactions with anaerobic digestion might affect energy recovery, which is typically overlooked. This work describes the current understanding of the occurrence and fate of food additives in anaerobic digestion of food waste. The biotransformation pathways of food additives during anaerobic digestion are well discussed. In addition, important discoveries in the effects and underlying mechanisms of food additives on anaerobic digestion are reviewed. The results showed that most of the food additives had negative effects on anaerobic digestion by deactivating functional enzymes, thus inhibiting methane production. By reviewing the response of microbial communities to food additives, we can further improve our understanding of the impact of food additives on anaerobic digestion. Intriguingly, the possibility that food additives may promote the spread of antibiotic resistance genes, and thus threaten ecology and public health, is highlighted. Furthermore, strategies for mitigating the effects of food additives on anaerobic digestion are outlined in terms of optimal operation conditions, effectiveness, and reaction mechanisms, among which chemical methods have been widely used and are effective in promoting the degradation of food additives and increasing methane production. This review aims to advance our understanding of the fate and impact of food additives in anaerobic digestion and to spark novel research ideas for optimizing anaerobic digestion of organic solid waste.

Buyang huanwu decoction inhibits diabetes-accelerated atherosclerosis via reduction of AMPK-Drp1-mitochondrial fission axis.

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese drugs, including Buyang Huanwu decoction (BYHWD), have been used in traditional practice to manage cardiovascular and cerebrovascular diseases. However, the effect and mechanisms by which this decoction alleviates diabetes-accelerated atherosclerosis are unknown and require exploration. AIM OF THE STUDY: This study aims to investigate the pharmacological effects of BYHWD on preventing diabetes-accelerated atherosclerosis, and elucidate its underlying mechanism. MATERIALS AND METHODS: Streptozotocin (STZ)-induced diabetic ApoE-/- mice were treated with BYHWD. Atherosclerotic aortic lesions, endothelial function, mitochondrial morphology, and mitochondrial dynamics-related proteins were evaluated in isolated aortas. High glucose-exposed human umbilical endothelial cells (HUVECs) were treated with BYHWD and its components. AMPK siRNA transfection, Drp1 molecular docking, Drp1 enzyme activity measurement, and so on were used to explore and verify the mechanism. RESULT: BYHWD treatment inhibited the worsening of diabetes-accelerated atherosclerosis by lessening atherosclerotic lesions in diabetic ApoE-/- mice, by impeding endothelial dysfunction under diabetic conditions, and by inhibiting mitochondrial fragmentation by lowering protein expression levels of Drp1 and mitochondrial fission-1 protein (Fis1) in diabetic aortic endothelium. In high glucose-exposed HUVECs, BYHWD treatment also downgraded reactive oxygen species, promoted nitric oxide levels, and abated mitochondrial fission by reducing protein expression levels of Drp1 and fis1, but not mitofusin-1 and optic atrophy-1. Interestingly, we found that BYHWD's protective effect against mitochondrial fission is mediated by AMPK activation-dependent reduction of Drp1 levels. The main serum chemical components of BYHWD, ferulic acid, and calycosin-7-glucoside, can reduce the expression of Drp1 by regulating AMPK, and can inhibit the activity of GTPase of Drp1. CONCLUSION: The above findings support the conclusion that BYHWD suppresses diabetes-accelerated atherosclerosis by reducing mitochondrial fission through modulation of the AMPK/Drp1 pathway.

Mindfulness-based intervention for clinical and subthreshold perinatal depression and anxiety: A systematic review and meta-analysis of randomized controlled trial.

OBJECTIVES: About one in four mothers will experience depression and anxiety during pregnancy and within their first year following childbirth. The meta-analysis aggregated the findings of randomized controlled trials (RCTs) evaluating the immediate post-intervention and maintenance effects of MBI on perinatal depression and anxiety. METHODS: A systematic search was conducted in PubMed, PsycINFO, Medline, Scopus, and Web of Science for English-language journal articles from the first available date until Oct 27th, 2022. RESULTS: Twenty-five published RCTs were identified and reviewed, with a total of 2495 perinatal women. MBI was superior to controls for clinical and subthreshold perinatal depression and anxiety. The benefit for depression reduction was stable over time and sustained to the postpartum period, but the maintenance effect on perinatal anxiety was less conclusive. Moreover, MBI's post-intervention effects on depression and anxiety were moderated by perinatal women's symptom severity. The post intervention effects were significantly greater among women in Low- and Middle-Income countries, where perinatal mental health care is less available and accessible. Greater improvement in mindfulness was also associated with a significantly larger post-intervention effect on perinatal depression. CONCLUSIONS: This meta-analysis suggests that MBIs may complement and extend the available range of effective interventions for clinical and subthreshold perinatal depression and anxiety.

COVID-19-associated monocytic encephalitis (CAME): histological and proteomic evidence from autopsy.

Severe neurological symptoms are associated with Coronavirus disease 2019 (COVID-19). However, the morphologic features, pathological nature and their potential mechanisms in patient brains have not been revealed despite evidence of neurotropic infection. In this study, neuropathological damages and infiltrating inflammatory cells were quantitatively evaluated by immunohistochemical staining, ultrastructural examination under electron microscopy, and an image threshold method, in postmortem brains from nine critically ill COVID-19 patients and nine age-matched cadavers of healthy individuals. Differentially expressed proteins were identified by quantitative proteomic assays. Histopathological findings included neurophagocytosis, microglia nodules, satellite phenomena, extensive edema, focal hemorrhage, and infarction, as well as infiltrating mononuclear cells. Immunostaining of COVID-19 brains revealed extensive activation of both microglia and astrocytes, severe damage of the blood-brain barrier (BBB) and various degrees of perivascular infiltration by predominantly CD14+/CD16+/CD141+/CCR7+/CD11c+ monocytes and occasionally CD4+/CD8+ T lymphocytes. Quantitative proteomic assays combined with bioinformatics analysis identified upregulated proteins predominantly involved in immune responses, autophagy and cellular metabolism in COVID-19 patient brains compared with control brains. Proteins involved in brain development, neuroprotection, and extracellular matrix proteins of the basement membrane were downregulated, potentially caused by the activation of transforming growth factor ß receptor and vascular endothelial growth factor signaling pathways. Thus, our results define histopathological and molecular profiles of COVID-19-associated monocytic encephalitis (CAME) and suggest potential therapeutic targets.

The Relationship Between Porphyromonas Gingivalis and Rheumatoid Arthritis: A Meta-Analysis.

Rheumatoid arthritis (RA) is a systematical autoimmune disease, characterized by chronic synovial joint inflammation and hurt. Porphyromonas gingivalis(P. gingivalis) can cause life-threatening inflammatory immune responses in humans when the host pathogenic clearance machinery is disordered. Some epidemiological studies have reported that P. gingivalis exposure would increase the prevalence of RA. However, the results remain inconsistent. Therefore, a meta-analysis was done to systematically analyze the relationship between P. gingivalis exposure and the prevalence of rheumatoid arthritis. Database including Cochrane Library, Web of Science, PubMed, and EMBASE were searched for published epidemiological articles assessed the relationship between P. gingivalis and RA. Obtained studies were screened based on the predefined inclusion and exclusion criteria. The overall Odds Ratios (ORs) of incorporated articles were pooled by random-effect model with STATA 15.1 software. The literature search returned a total of 2057 studies. After exclusion, 28 articles were included and analyzed. The pooled ORs showed a significant increase in the risk of RA in individuals with P. gingivalis exposure (OR = 1.86; 95% CI: 1.43-2.43). Subgroup analysis revealed that pooled ORs from populations located in Europe (OR = 2.17; 95% CI: 1.46-3.22) and North America (OR = 2.50; 95% CI: 1.23-5.08) were significantly higher than that from population in Asia (OR = 1.11; 95% CI: 1.03-1.20). Substantial heterogeneity was observed but did not significantly influence the overall outcome. In conclusion, our results indicated P. gingivalis exposure was a risk factor in RA. Prompt diagnosis and management decisions on P. gingivalis antimicrobial therapy would prevent rheumatoid arthritis development and progression.

Spatially resolved proteomic map shows that extracellular matrix regulates epidermal growth.

Human skin comprises stratified squamous epithelium and dermis with various stromal cells and the extracellular matrix (ECM). The basement membrane (BM), a thin layer at the top of the dermis, serves as a unique niche for determining the fate of epidermal stem cells (EpSCs) by transmitting physical and biochemical signals to establish epidermal cell polarity and maintain the hierarchical structure and function of skin tissue. However, how stem cell niches maintain tissue homeostasis and control wound healing by regulating the behavior of EpSCs is still not completely understood. In this study, a hierarchical skin proteome map is constructed using spatial quantitative proteomics combined with decellularization, laser capture microdissection, and mass spectrometry. The specific functions of different structures of normal native skin tissues or tissues with a dermatologic disease are analyzed in situ. Transforming growth factor-beta (TGFß)-induced protein ig-h3 (TGFBI), an ECM glycoprotein, in the BM is identified that could enhance the growth and function of EpSCs and promote wound healing. Our results provide insights into the way in which ECM proteins facilitate the growth and function of EpSCs as part of an important niche. The results may benefit the clinical treatment of skin ulcers or diseases with refractory lesions that involve epidermal cell dysfunction and re-epithelialization block in the future.