Preliminary Study on Clinical Characteristics and Pathogenesis of IQSEC2 Mutations Patients.

Background: The IQ motif and Sec7 domain ArfGEF 2 (IQSEC2), an X-linked gene that encodes the BRAG1 protein, is a guanine nucleotide exchange factor for the ADP ribosylation factor (ARF) protein family in the small guanosine triphosphate (GTP) binding protein. Mutations in this gene result in disorders such as intellectual disability (ID) and epilepsy. In this study, we analyze the clinical features of two patients with IQSEC2-mutation-related disease and discuss their possible pathogenesis. Methods: The two patients were diagnosed with ID and epilepsy. Genetic testing was performed using whole-exome sequencing, and the three-dimensional protein structure was analyzed. UCSC Genome Browser was used to analyze the conservation of IQSEC2 in different species. We compared IQSEC2 expression in the proband families with that in a control group, as well as the expression of the postsynaptic identity protein 95 (PSD-95), synapse-associated protein 97 (SAP97), ADP ribosylation factor 6 (ARF-6), and insulin receptor substrate 53kDa (IRSP53) genes interacting with IQSEC2. Results: We identified two semi-zygote mutations located in conserved positions in different species: an unreported de novo mutation, C.3576C>A (p. Tyr1192*), and a known mutation, c.2983C>T (p. Arg995Trp). IQSEC2 mutations resulted in significant changes in the predicted three-dimensional protein structure, while its expression in the two probands was significantly lower than that in the age-matched control group, and IQSEC2 expression in proband 1 was lower than that in his family members. The expression levels of PSD-95, ARF-6, and SAP97, IRSP 53, which interact with IQSEC2, were also significantly different from those in the family members and age-matched healthy children. Conclusion: The clinical phenotype resulting from IQSEC2 mutations can be explained by the significant decrease in its expression, loss of function of the mutant protein, and change in the expression of related genes. Our results provide novel insights into the molecular phenotype conferred by the IQSEC2 variants.

A bibliometric perspective on the occurrence and migration of microplastics in soils amended with sewage sludge.

The land application of sewage sludge from wastewater treatment plants has been recognized as a major source of microplastic contamination in soil. Nevertheless, the fate and behavior of microplastics in soil remain uncertain, particularly their distribution and transport, which are poorly understood. This study does a bibliometric analysis and visualization of relevant research publications using the CiteSpace software. It explores the limited research available on the topic, highlighting the potential for it to emerge as a research hotspot in the future. Chinese researchers and institutions are paying great attention to this field and are promoting close academic cooperation among international organizations. Current research hot topics mainly involve microplastic pollution caused by the land application of sewage sludge, as well as the detection, environmental fate, and removal of microplastics in soil. The presence of microplastics in sludge, typically ranging from tens of thousands to hundreds of thousands of particles (p)/kg, inevitably leads to their introduction into soil upon land application. In China, the estimated annual accumulation of microplastics in the soil due to sludge use is approximately 1.7 × 1013 p. In European countries, the accumulation ranges from 8.6 to 71 × 1013 p. Sludge application has significantly elevated soil microplastic concentrations, with higher application rates and frequencies resulting in up to several-fold increases. The primary forms of microplastics found in soils treated with sludge are fragments and fibers, primarily in white color. These microplastics consist primarily of components such as polyamide, polyethylene, and polypropylene. The vertical transport behavior of microplastics is influenced by factors such as tillage, wind, rainfall, bioturbation, microplastic characteristics (e.g., fraction, particle size, and shape), and soil physicochemical properties (e.g., organic matter, porosity, electrical conductivity, and pH). Research indicates that microplastics can penetrate up to 90 cm into the soil profile and persist for decades. Microplastics in sewage sludge-amended soils pose potential long-term threats to soil ecosystems and even human health. Future research should focus on expanding the theoretical understanding of microplastic behavior in these soils, enabling the development of comprehensive risk assessments and informed decision-making for sludge management practices. PRACTITIONER POINTS: Microplastics in sewage sludge range from tens to hundreds of thousands per kilogram. Sludge land application contributes significantly to soil microplastic pollution. The main forms of microplastics in sludge-amended soils are fragments and fibers. Microplastics are mainly composed of polyamide, polyethylene, and polypropylene. Microplastics can penetrate up to 90 cm into the soil profile and persist for decades.

Erratum: Activation of Nrf2 Attenuates Pulmonary Vascular Remodeling via Inhibiting Endothelial-to-Mesenchymal Transition: an Insight from a Plant Polyphenol: Erratum.

[This corrects the article DOI: 10.7150/ijbs.20316.].

FBXL4 mutations cause excessive mitophagy via BNIP3/BNIP3L accumulation leading to mitochondrial DNA depletion syndrome.

Mitochondria are essential organelles found in eukaryotic cells that play a crucial role in ATP production through oxidative phosphorylation (OXPHOS). Mitochondrial DNA depletion syndrome (MTDPS) is a group of genetic disorders characterized by the reduction of mtDNA copy number, leading to deficiencies in OXPHOS and mitochondrial functions. Mutations in FBXL4, a substrate-binding adaptor of Cullin 1-RING ubiquitin ligase complex (CRL1), are associated with MTDPS, type 13 (MTDPS13). Here, we demonstrate that, FBXL4 directly interacts with the mitophagy cargo receptors BNIP3 and BNIP3L, promoting their degradation through the ubiquitin-proteasome pathway via the assembly of an active CRL1FBXL4 complex. However, MTDPS13-associated FBXL4 mutations impair the assembly of an active CRL1FBXL4 complex. This results in a notable accumulation of BNIP3/3L proteins and robust mitophagy even at basal levels. Excessive mitophagy was observed in Knockin (KI) mice carrying a patient-derived FBXL4 mutation and cortical neurons (CNs)-induced from MTDPS13 patient human induced pluripotent stem cells (hiPSCs). In summary, our findings suggest that abnormal activation of BNIP3/BNIP3L-dependent mitophagy impairs mitochondrial homeostasis and underlies FBXL4-mutated MTDPS13.

Clinical features and underlying mechanisms of KAT6B disease in a Chinese boy.

BACKGROUND: Lysine acetyltransferase 6B (KAT6B) encodes a highly conserved histone acetyltransferase that regulates the expression of multiple genes and is essential for human growth and development. METHODS: We identified a novel frameshift variant c.3185del (p.leu1062Argfs*52) in a 5-year-old Chinese boy and further analyzed KAT6B expression and its interacting complexes and downstream products using real-time quantitative polymerase chain reaction (qPCR). Furthermore, we assessed its three-dimensional protein structure and compared the variant with other reported KAT6B variants. RESULTS: The deletion changed the leucine at position 1062 into an arginine, resulting in translation termination after base 3340, which may have affected protein stability and protein-protein interactions. KAT6B mRNA expression levels in this case were substantially different from those of the parents and controls in the same age range. There were also significant differences in mRNA expression levels among affected children's parents. RUNX2 and NR5A1, downstream products of the gene, affect the corresponding clinical symptoms. The mRNA expression levels of the two in children were lower than those of their parents and controls in the same age range. CONCLUSION: This deletion in KAT6B may affect protein function and cause corresponding clinical symptoms through interactions with key complexes and downstream products.

Cell Death Pathways: The Variable Mechanisms Underlying Fine Particulate Matter-Induced Cytotoxicity.

Recently, the advent of health risks due to the cytotoxicity of fine particulate matter (FPM) is concerning. Numerous studies have reported abundant data elucidating the FPM-induced cell death pathways. However, several challenges and knowledge gaps are still confronted nowadays. On one hand, the undefined components of FPM (such as heavy metals, polycyclic aromatic hydrocarbons, and pathogens) are all responsible for detrimental effects, thus rendering it difficult to delineate the specific roles of these copollutants. On the other hand, owing to the crosstalk and interplay among different cell death signaling pathways, precisely determining the threats and risks posed by FPM is difficult. Herein, we recapitulate the current knowledge gaps present in the recent studies regarding FPM-induced cell death, and propose future research directions for policy-making to prevent FPM-induced diseases and improve knowledge concerning the adverse outcome pathways and public health risks of FPM.

The ketogenic diet for Dravet syndrome: A multicenter retrospective study.

OBJECTIVE: The ketogenic diet (KD) is one of the main treatments for drug-resistant epilepsy. However, there have been few multicenter reports on the use of the KD for the treatment of Dravet syndrome (DS). The aim of this study was to analyze the efficacy and safety of this approach based on a large number of multicenter cases. METHODS: This was a retrospective, multicenter cohort study from 14 centers in China. All patients were treated with the KD. We compared the effects of KD intervention time, age, and other factors. RESULTS: From March 2014 to March 2020, we treated 114 patients with DS with the KD. The male-to-female ratio was 67:47. The KD median initiation age was 3 y and 4 mo, and the median number of antiseizure medications (ASMs) was 2.4. KD therapy was the first choice for three patients. Exactly 10.5% of the patients started KD therapy after failure of the first ASM therapy, with 35.1% after failure of the second, 44.7% after the third, and 7% after the fourth or more. After KD therapy for 1, 3, 6, and 12 mo, the seizure-free rates were 14%, 32.5%, 30.7%, and 19.3%, respectively; KD efficacy (≥50% reduction in seizure frequency) were 57.9%, 76.3%, 59.6%, and 43%, respectively; the retention rates were 97.4%, 93%, 71.9%, and 46.5%, respectively; and the rates of adverse events were 25.2%, 19.9%, 11%, and 5.7%, respectively. CONCLUSIONS: Real-world, multicenter data analysis showed that the KD is effective for patients with DS and has a low incidence of side effects.

Natural Products for the Treatment of Pulmonary Hypertension: Mechanism, Progress, and Future Opportunities.

Pulmonary hypertension (PH) is a lethal disease due to the remodeling of pulmonary vessels. Its pathophysiological characteristics include increased pulmonary arterial pressure and pulmonary vascular resistance, leading to right heart failure and death. The pathological mechanism of PH is complex and includes inflammation, oxidative stress, vasoconstriction/diastolic imbalance, genetic factors, and ion channel abnormalities. Currently, many clinical drugs for the treatment of PH mainly play their role by relaxing pulmonary arteries, and the treatment effect is limited. Recent studies have shown that various natural products have unique therapeutic advantages for PH with complex pathological mechanisms owing to their multitarget characteristics and low toxicity. This review summarizes the main natural products and their pharmacological mechanisms in PH treatment to provide a useful reference for future research and development of new anti-PH drugs and their mechanisms.

Deciphering the Mechanism of Wogonin, a Natural Flavonoid, on the Proliferation of Pulmonary Arterial Smooth Muscle Cells by Integrating Network Pharmacology and In Vitro Validation.

Wogonin is one of the main active components of Scutellaria baicalensis, which has anti-inflammatory, anti-angiogenesis, and anti-fibrosis effects. Nevertheless, the effect of wogonin on pulmonary hypertension (PH) still lacks systematic research. This study aims to elucidate the potential mechanism of wogonin against PH through network pharmacology and further verify it through biological experiments in pulmonary arterial smooth muscle cells (PASMCs). The potential targets and pathways of wogonin against PH were predicted and analyzed by network pharmacology methods and molecular docking technology. Subsequently, the proliferation of PASMCs was induced by platelet-derived growth factor-BB (PDGF-BB). Cell viability and migration ability were examined. The method of Western blot was adopted to analyze the changes in related signaling pathways. Forty potential targets related to the effect of wogonin against PH were obtained. Based on the protein-protein interaction (PPI) network, gene-ontology (GO) and Kyoto encyclopedia of genes and genomes (KEGG) enrichment, and molecular docking, it was shown that the effect of wogonin against PH is closely related to the proliferation of PASMCs and the hypoxia-inducible factor-1α (HIF-1α) pathway. A variety of results from biological experiments verified that wogonin can effectively inhibit the proliferation, migration, and phenotypic transformation of PDGF-BB-mediated PASMCs. In addition, the anti-proliferation effect of wogonin may be achieved by regulating HIF-1/ NADPH oxidase 4 (NOX4) pathway.

Extra-Pulmonary Translocation of Exogenous Ambient Nanoparticles in the Human Body.

As one of the major pollutants in the air, ambient fine particles are gaining considerable attention in terms of public health concerns. Significant progress has been achieved in recent years in understanding the biological effects and mechanisms of ambient fine particles. The airborne particles can enter the human body through various pathways and translocate to a range of different organs and further stay in these organs for extended periods. Current studies are making substantial achievements, while many challenges remain. On one hand, the whole picture of the concurrent exposure pathways and the translocation of particles in the human body should be explored, requiring technological advances and systematic biobanking of human samples for analysis. On the other hand, the correlation between the environmental exposure concentration of ambient particles and internal fate (i.e., dose, distribution patterns, and kinetics) of invasive particles needs to be investigated. Moreover, the biotransformation of particles in vivo should be considered, and more information is needed to differentiate exogenous particles from biological macromolecules and biogenically formed particles. We recapitulate the current knowledge gaps in understanding the fate of exogenous ambient fine particles in extra-pulmonary organs of the human body and the related biological effects and also propose future research directions to support both fundamental studies and policy making.

Clinical characteristics and genetics of ten Chinese children with PRRT2-associated neurological diseases.

Background: Proline-rich transmembrane protein 2 (PRRT2) plays an important role in the central nervous system and mutations in the gene are implicated in a variety of neurological disorders. This study aimed to summarize the clinical characteristics and gene expression analysis of neurological diseases related to the PRRT2 gene and explore the clinical characteristics, therapeutic effects, and possible pathogenic mechanisms of related diseases. Methods: We enrolled 10 children with PRRT2 mutation-related neurological diseases who visited the Children's Hospital affiliated with the Shanghai Jiaotong University School of Medicine/Shanghai Children's Hospital between May 2017 and February 2022. Video electroencephalography (VEEG), cranial imaging, treatment regimens, gene results, and gene expression were analyzed. Genetic testing involved targeted sequencing or whole-exome genome sequencing (WES). We further analyzed the expression and mutation conservation of PRRT2 and synaptosome-associated protein 25 (SNAP25) in blood samples using quantitative polymerase chain reaction (qPCR) and predicted the protein structure. Summary analysis of the reported gene maps and domains was also performed. Results: Ten children with PRRT2 gene mutations were analyzed, and 4 mutations were identified, consisting of 2 new (c.518A > C, p.Glu173 Ala; c.879 + 112G > A, p.?) and two known (c. 649 dup, p. Arg217Profs * 8; c. 649 del, p. Arg217Glufs * 12) mutations. Among these mutations, one was de novo(P6), and three could not be determined because one parent refused genetic testing. The clinical phenotypes were paroxysmal kinesigenic dyskinesia (PKD), benign familial infantile epilepsy (BFIE), epilepsy, infantile spasms, and intellectual disability. The qPCR results showed that PRRT2 gene expression levels were significantly lower in children and parent carriers than the control group. The SNAP25 gene expression level of affected children was significantly lower (P ≤ 0.001) than that of the control group. The mutation sites reported in this study are highly conserved in different species. Among the various drugs used, oxcarbazepine and sodium valproate were the most effective. All 10 children had a good disease prognosis, and 8 were completely controlled with no recurrence, whereas 2 had less severe and fewer seizures. Conclusion: Mutation of PRRT2 led to a significant decrease in its protein expression level and that of SNAP25, suggesting that the mutant protein may lead to the loss of its function and that of related proteins. This mutation site is highly conserved in most species, and there was no significant correlation between specific PRRT2 genotypes and clinical phenotypes. Asymptomatic carriers also have decreased gene expression levels, suggesting that more factors are involved.

Segawa syndrome caused by TH gene mutation and its mechanism.

Dopa-responsive dystonia (DRD), also known as Segawa syndrome, is a rare neurotransmitter disease. The decrease in dopamine caused by tyrosine hydroxylase (TH) gene mutation may lead to dystonia, tremor and severe encephalopathy in children. Although the disease caused by recessive genetic mutation of the tyrosine hydroxylase (TH) gene is rare, we found that the clinical manifestations of seven children with tyrosine hydroxylase gene mutations are similar to dopa-responsive dystonia. To explore the clinical manifestations and possible pathogenesis of the disease, we analyzed the clinical data of seven patients. Next-generation sequencing showed that the TH gene mutation in three children was a reported homozygous mutation (c.698G>A). At the same time, two new mutations of the TH gene were found in other children: c.316_317insCGT, and c.832G>A (p.Ala278Thr). We collected venous blood from four patients with Segawa syndrome and their parents for real-time quantitative polymerase chain reaction analysis of TH gene expression. We predicted the structure and function of proteins on the missense mutation iterative thread assembly refinement (I-TASSER) server and studied the conservation of protein mutation sites. Combined with molecular biology experiments and related literature analysis, the qPCR results of two patients showed that the expression of the TH gene was lower than that in 10 normal controls, and the expression of the TH gene of one mother was lower than the average expression level. We speculated that mutation in the TH gene may clinically manifest by affecting the production of dopamine and catecholamine downstream, which enriches the gene pool of Segawa syndrome. At the same time, the application of levodopa is helpful to the study, diagnosis and treatment of Segawa syndrome.

Clinical characteristics and prognosis of pediatric myelin oligodendrocyte glycoprotein antibody-associated diseases in China.

BACKGROUND: Research on myelin oligodendrocyte glycoprotein antibody (MOG-Ab)-associated disease (MOGAD) among Chinese children is relatively rare. Therefore, this study aimed to explore and analyze the clinical characteristics and prognoses of Chinese children with acquired demyelinating syndromes (ADSs) who tested positive or negative for MOG-Ab. METHODS: The clinical data of children with MOGAD who were treated in the Department of Neurology at Shanghai Children's Hospital from January 2017 to October 2021 were retrospectively collected. RESULTS: Among 90 children with ADSs, 30 were MOG-Ab-positive, and 60 were MOG-Ab-negative. MOG-Ab-positive children experienced more prodromal infections than did MOG-Ab-negative children (P < 0.05). Acute disseminated encephalomyelitis was the most common ADSs in both groups. There were ten cases of a rebound increase in MOG-Ab titers. There were significant differences in the MOG titer-related prognosis and disease time course between the disease relapse group and the non-relapse group (P < 0.01). Among the MOG-Ab-positive patients, the most affected brain areas detected via magnetic resonance imaging (MRI) were the temporal lobe, cerebellar hemispheres, brainstem, and periventricular lesions. The most common shapes of the lesions were commas, triangles, or patches. The average improvement time based on brain MRI was much longer in MOG-Ab-positive than in MOG-Ab-negative children (P < 0.05). The initial treatment time correlated with the disease time course, and the prognosis may be affected by the disease time course and serum MOG-Ab titer (P < 0.05). CONCLUSION: The clinical characteristics and imaging features of ADSs differed between MOG-Ab-positive and MOG-Ab-negative children. In addition to existing treatment plans, additional diagnoses and treatment plans should be developed to reduce recurrence and improve the prognoses of children with MOGAD.

Probing the Potential Mechanism of Quercetin and Kaempferol against Heat Stress-Induced Sertoli Cell Injury: Through Integrating Network Pharmacology and Experimental Validation.

Quercetin and kaempferol are flavonoids widely present in fruits, vegetables, and medicinal plants. They have attracted much attention due to their antioxidant, anti-inflammatory, anticancer, antibacterial, and neuroprotective properties. As the guarantee cells in direct contact with germ cells, Sertoli cells exert the role of support, nutrition, and protection in spermatogenesis. In the current study, network pharmacology was used to explore the targets and signaling pathways of quercetin and kaempferol in treating spermatogenic disorders. In vitro experiments were integrated to verify the results of quercetin and kaempferol against heat stress-induced Sertoli cell injury. The online platform was used to analyze the GO biological pathway and KEGG pathway. The results of the network pharmacology showed that quercetin and kaempferol intervention in spermatogenesis disorders were mostly targeting the oxidative response to oxidative stress, the ROS metabolic process and the NFκB pathway. The results of the cell experiment showed that Quercetin and kaempferol can prevent the decline of cell viability induced by heat stress, reduce the expression levels of HSP70 and ROS in Sertoli cells, reduce p-NF-κB-p65 and p-IκB levels, up-regulate the expression of occludin, vimentin and F-actin in Sertoli cells, and protect cell structure. Our research is the first to demonstrate that quercetin and kaempferol may exert effects in resisting the injury of cell viability and structure under heat stress.

Co-Exposure of Ambient Particulate Matter and Airborne Transmission Pathogens: The Impairment of the Upper Respiratory Systems.

Recent evidence has pinpointed the positive relevance between air particulate matter (PM) pollution and epidemic spread. However, there are still significant knowledge gaps in understanding the transmission and infection of pathogens loaded on PMs, for example, the interactions between pathogens and pre-existing atmospheric PM and the health effects of co-exposure on the inhalation systems. Here, we unraveled the interactions between fine particulate matter (FPM) and Pseudomonas aeruginosa (P. aeruginosa) and evaluated the infection and detrimental effects of co-exposure on the upper respiratory systems in both in vitro and in vivo models. We uncovered the higher accessibility and invasive ability of pathogens to epithelial cells after loading on FPMs, compared with the single exposure. Furthermore, we designed a novel laboratory exposure model to simulate a real co-exposure scenario. Intriguingly, the co-exposure induced more serious functional damage and longer inflammatory reactions to the upper respiratory tract, including the nasal cavity and trachea. Collectively, our results provide a new point of view on the transmission and infection of pathogens loaded on FPMs and uncover the in vivo systematic impairments of the inhalation tract under co-exposure through a novel laboratory exposure model. Hence, this study sheds light on further investigations of the detrimental effects of air pollution and epidemic spread.

Two heterozygous mutations in the calcium/calmodulin-dependent serine protein kinase gene (CASK) in cases with developmental disorders.

BACKGROUND: The calcium/calmodulin-dependent serine protein kinase gene (CASK) is an essential gene in mammals, critical for neurodevelopment. The purpose of this study is to expand the understanding of the diagnosis of CASK-linked disorders. MATERIALS/METHODS: From clinical and genetic mutational analyses, relevant data in 2 Han Chinese patients were collected and analyzed. Real-time quantitative PCR (RT-qPCR) was performed to investigate the CASK expression levels in the patients. The X-chromosome inactivation (XCI) patterns of the patients and their nuclear families were tested by quantitation of methylation of the polymorphic human androgen receptor (HUMARA) locus. RESULTS: Two Han Chinese patients both presented with intellectual disability (ID), microcephaly with pontine and cerebellar hypoplasia (MICPCH). Two de novo mutations of c.82C>T (p.Arg28*) and c.846C>G (p.Tyr282*) in CASK have been investigated and predicted to be deleterious, which have produced truncated proteins. The functional protein association network of STRING (http://string-db.org) generated three-dimensional (3D) atomic models based on protein sequences in CASK and two Arg28 and Tyr282 residues were marked. RT-qPCR showed lower copy numbers of CASK expression in the patients than in their parents, as well as the sex- and age- matched control groups. Patient 1 showed a skewed XCI pattern, while no related changes noted in patient 2. CONCLUSIONS: Patients carrying different nonsense variants may have different degrees of different clinical phenotypes. This study expands the spectrum of genotype and phenotype correlations of CASK-linked disorders in the Han Chinese ethnicity and provides new insights into the molecular mechanism.

The Study on the Clinical Phenotype and Function of HPRT1 Gene.

Background: Lesch-Nyhan disease (LND) is a rare x-linked purine metabolic neurogenetic disease caused by enzyme hypoxanthine-guanine phosphoriribosyltransferase(HGprt) deficiency, also known as self-destructive appearance syndrome. A series of manifestations are caused by abnormal purine metabolism. The typical clinical manifestations are hyperuricemia, growth retardation, mental retardation, short stature, dance-like athetosis, aggressive behavior, and compulsive self-harm. Methods: We identified a point mutation c.151C > T (p. Arg51*) in a pedigree. We analyzed the clinical characteristics of children in a family, and obtained the blood of their parents and siblings for second-generation sequencing. At the same time, we also analyzed and compared the expression of HPRT1 gene and predicted the three-dimensional structure of the protein. And we analyzed the clinical manifestations caused by the defect of the HPRT1 gene. Results: The mutation led to the termination of transcription at the 51st arginine, resulting in the production of truncated protein, and the relative expression of HPRT1 gene in patients was significantly lower than other family members and 10 normal individuals. Conclusion: This mutation leads to the early termination of protein translation and the formation of a truncated HPRT protein, which affects the function of the protein and generates corresponding clinical manifestations.

Mechanistic and therapeutic perspectives of baicalin and baicalein on pulmonary hypertension: A comprehensive review.

Pulmonary hypertension (PH) is a chronic and fatal disease, for which new therapeutic drugs and approaches are needed urgently. Baicalein and baicalin, the active compounds of the traditional Chinese medicine, Scutellaria baicalensis Georgi, exhibit a wide range of pharmacological activities. Numerous studies involving in vitro and in vivo models of PH have revealed that the treatment with baicalin and baicalein may be effective. This review summarizes the potential mechanisms driving the beneficial effects of baicalin and baicalein treatment on PH, including anti-inflammatory response, inhibition of pulmonary smooth muscle cell proliferation and endothelial-to-mesenchymal transformation, stabilization of the extracellular matrix, and mitigation of oxidative stress. The pharmacokinetics of these compounds have also been reviewed. The therapeutic potential of baicalin and baicalein warrants their continued study as natural treatments for PH.

Induced pluripotent stem cells (SHCDNi006-A cells) isolated from the peripheral blood mononuclear cells of a five-month-old Chinese girl with the heterozygous missense mutation (c.2800 G>A) in the KCNT1 gene.

Epilepsy of infancy with migrating focal seizures (EIMFS) is a kind of epileptic encephalopathy with high genetic heterogeneity. The most common pathogenic gene for EIMFS is potassium sodium-activated channel subfamily T member 1 (KCNT1). Using Sendai virus-mediated reprogramming, we established an induced pluripotent stem cell (iPSC) line from the peripheral blood mononuclear cells (PBMCs) of a five-month-old Chinese girl with heterozygous missense mutation (c.2800 G>A) in the KCNT1 gene. The iPSCs were stable during amplification, expressed pluripotent genes, maintained a normal karyotype, and showed characteristics of the three germs layers in an in vitro differentiation assay.

Immunity and inflammation in pulmonary arterial hypertension: From pathophysiology mechanisms to treatment perspective.

Pulmonary arterial hypertension (PAH) is a severe cardiopulmonary dysfunctional disease, characterized by progressive vascular remodeling. Inflammation is an increasingly recognized feature of PAH, which is important for the initiation and maintenance of vascular remodeling. High levels of various inflammatory mediators have been documented in both PAH patients and experimental models of PAH. Similarly, multiple immune cells were found to accumulate in and around the wall of remodeled pulmonary vessels and in the vicinity of plexiform lesions, respectively. On the other hand, inflammation is also a bridge from autoimmune diseases to PAH. Autoimmune diseases always lead to chronic inflammation, characterized by the low-level persistent infiltration of immune cells, and elevated levels of several pro-inflammatory cytokines and chemokines. In addition, circulating autoantibodies are found in the peripheral blood of patients, indicating a possible role of autoimmunity in the pathogenesis of PAH. Thus, anti-inflammatory and immunotherapy might be new strategies to prevent or even reverse the process of PAH. Many anti-inflammatory agents and immunotherapies have been confirmed in animal models while some clinical trials employing immunotherapies are completed or currently underway. Here, we review pathological mechanisms associated with inflammation and immunity in the development of PAH, and discuss potential interventions for the treatment of PAH.