FUBP3 mediates the amyloid-β-induced neuronal NLRP3 expression

Alzheimer's disease is characterized by deposition of amyloid-β,which forms extracellular neuritic plaques,and accumulation of hyperphosphorylated tau,which aggregates to form intraneuronal neurofibrillary tangles,in the brain.The NLRP3 inflammasome may play a role in the transition from amyloid-βdeposition to tau phosphorylation and aggregation.Because NLRP3 is primarily found in brain microglia,and tau is predominantly located in neurons,it has been suggested that NLRP3 expressed by microglia indirectly triggers tau phosphorylation by upregulating the expression of pro-inflammatory cytokines.Here,we found that neurons also express NLRP3 in vitro and in vivo,and that neuronal NLRP3 regulates tau phosphorylation.Using biochemical methods,we mapped the minimal NLRP3 promoter and identified FUBP3 as a transcription factor regulating NLRP3 expression in neurons.In primary neurons and the neuroblastoma cell line Neuro2A,FUBP3 is required for endogenous NLRP3 expression and tau phosphorylation only when amyloid-βis present.In the brains of aged wild-type mice and a mouse model of Alzheimer's disease,FUBP3 expression was markedly increased in cortical neurons.Transcriptome analysis suggested that FUBP3 plays a role in neuron-mediated immune responses.We also found that FUBP3 trimmed the 5′end of DNA fragments that it bound,implying that FUBP3 functions in stress-induced responses.These findings suggest that neuronal NLRP3 may be more directly involved in the amyloid-β-to–phospho-tau transition than microglial NLRP3,and that amyloid-βfundamentally alters the regulatory mechanism of NLRP3 expression in neurons.Given that FUBP3 was only expressed at low levels in young wild-type mice and was strongly upregulated in the brains of aged mice and Alzheimer's disease mice,FUBP3 could be a safe therapeutic target for preventing Alzheimer's disease progression.

Nomogram to predict severe retinopathy of prematurity in Southeast China

AIM:To define the predictive factors of severe retinopathy of prematurity(ROP)and develop a nomogram for predicting severe ROP in southeast China.METHODS:Totally 554 infants diagnosed with ROP hospitalized in the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University and hospitalized in Taizhou Women and Children’s Hospital were included.Clinical data and 43 candidate predictive factors of ROP infants were collected retrospectively.Logistic regression model was used to identify predictive factors of severe ROP and to propose a nomogram for individual risk prediction,which was compared with WINROP model and Digirop-Birth model.RESULTS:Infants from the Second Affiliated Hospital and Yuying Children’s Hospital of Wenzhou Medical University(n=478)were randomly allocated into training(n=402)and internal validation group(n=76).Infants from Taizhou Women and Children’s Hospital were set as external validation group(n=76).Severe ROP were found in 52 of 402 infants,12 of 76 infants,and 7 of 76 infants in training group,internal validation group,and external validation group,respectively.Birth weight[odds ratio(OR),0.997;95%confidence interval(CI),0.996-0.999;P<0.001],multiple births(OR,1.885;95%CI,1.013-3.506;P=0.045),and non-invasive ventilation(OR,0.288;95%CI,0.146-0.570;P<0.001)were identified as predictive factors for the prediction of severe ROP,by univariate analysis and multivariate analysis.For predicting severe ROP based on the internal validation group,the areas under receiver operating characteristic curve(AUC)was 78.1(95%CI,64.2-92.0)for the nomogram,32.9(95%CI,15.3-50.5)for WINROP model,70.2(95%CI,55.8-84.6)for Digirop-Birth model.In external validation group,AUC of the nomogram was also higher than that of WINROP model and Digirop-Birth model(80.2 versus 51.1 and 63.4).The decision curve analysis of the nomogram demonstrated better clinical efficacy than that of WINROP model and Digirop-Birth model.The calibration curves demonstrated a good consistency between the actual severe ROP incidence and the predicted probability.CONCLUSION:Birth weight,multiple births,and noninvasive ventilation are independent predictors of severe ROP.The nomogram has a good ability to predict severe ROP and performed well on internal validation and external validation in southeast China.

Basilic vein variation encountered during surgery for arm vein port:A case report

BACKGROUND Venous variations are uncommon and usually hard to identify,and basilic vein variation is particularly rare.Basilic vein variation usually presents without any clinical symptoms and is often regarded as a benign alteration.This case was a patient with congenital basilic vein variation encountered during surgery for an infusion port.CASE SUMMARY We documented and analyzed an uncommon anatomical variation in the basilic vein encountered during arm port insertion.This peculiarity has hitherto remained undescribed in the literature.We offer remedial strategies for addressing this anomaly in the future and precautionary measures to circumvent its occurrence.We conducted a comprehensive review of analogous cases in the literature,offering pertinent therapeutic recommendations and solutions,with the aim of enhancing the efficacy and safety of future arm port implantations.CONCLUSION Venous variation is rare and requires detailed intraoperative and postoperative examination to ensure accuracy,so as not to affect subsequent treatment.

Dialectical study of disulfidptosis and clinical outcome in patients with colorectal cancer

Background:Colorectal cancer(CRC)is a leading cause of cancer mortality globally.This study aims to develop a prognostic model based on disulfidptosis-related genes to assess survival outcomes in CRC,highlighting the tumor microenvironment’s role.Methods:The thought of traditional Chinese medicine syndrome differentiation and treatment runs through the whole study.We analyzed CRC tissue data from The Cancer Genome Atlas and the Gene Expression Omnibus using single-sample gene set enrichment and weighted gene correlation network analyses to identify prognostic markers and evaluate immune infiltration.We also investigated predictive drug sensitivities.Results:We identified seven disulfidptosis-related markers–complement C1q A chain(C1QA),solute carrier family 11 member 1(SLC11A1),cluster of differentiation 36(CD36),cluster of differentiation 6(CD6),interleukin 1 receptor associated kinase 3(IRAK3),S100 calcium binding protein A8(S100A8),and CD8 subunit alpha(CD8A)–that significantly influence prognosis.Patients classified in the low-risk group demonstrated improved overall survival compared to those in the high-risk group across training(P=0.0026)and validation cohorts(P=0.032).Differential gene expression was significant in the high-risk group(P<0.001),and prevalent mutations included APC regulator of WNT signaling pathway(APC),tumor protein P53(TP53),Titin(TTN),and Kirsten rat sarcoma viral oncogene(KRAS).The risk score correlated linearly with tumor microenvironment attributes.The results of drug analysis showed that some traditional drugs may have anticancer effects through the vertical action of disulfidptosis.Conclusion:Our prognostic model,integrating seven disulfidptosis-related genes,categorizes CRC patients by survival probability and underscores these genes as potential biomarkers linked to the tumor microenvironment.These findings support their use in refining therapeutic strategies for CRC.

Propofol postconditioning ameliorates hypoxia/reoxygenation induced H9c2 cell apoptosis and autophagy via upregulating forkhead transcription factors under hyperglycemia

Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.

Chlorogenic acid alleviates hypoxic-ischemic brain injury in neonatal mice

Recent studies have shown that chlorogenic acid(CGA),which is present in coffee,has protective effects on the nervous system.However,its role in neonatal hypoxic-ischemic brain injury remains unclear.In this study,we established a newborn mouse model of hypoxic-ischemic brain injury using a modified Rice-Vannucci method and performed intraperitoneal injection of CGA.We found that CGA intervention effectively reduced the volume of cerebral infarct,alleviated cerebral edema,restored brain tissue structure after injury,and promoted axon growth in injured brain tissue.Moreover,CGA pretreatment alleviated oxygen-glucose deprivation damage of primary neurons and promoted neuron survival.In addition,changes in ferroptosis-related proteins caused by hypoxic-ischemic brain injury were partially reversed by CGA.Furthermore,CGA intervention upregulated the expression of the key ferroptosis factor glutathione peroxidase 4 and its upstream glutamate/cystine antiporter related factors SLC7A11 and SLC3A2.In summary,our findings reveal that CGA alleviates hypoxic-ischemic brain injury in neonatal mice by reducing ferroptosis,providing new ideas for the treatment of neonatal hypoxic-ischemic brain injury.

Pathological mechanisms and therapeutic outlooks for arthrofibrosis

Arthrofibrosis is a fibrotic joint disorder that begins with an inflammatory reaction to insults such as injury,surgery and infection.Excessive extracellular matrix and adhesions contract pouches,bursae and tendons,cause pain and prevent a normal range of joint motion,with devastating consequences for patient quality of life.Arthrofibrosis affects people of all ages,with published rates varying.The risk factors and best management strategies are largely unknown due to a poor understanding of the pathology and lack of diagnostic biomarkers.However,current research into the pathogenesis of fibrosis in organs now informs the understanding of arthrofibrosis.The process begins when stress signals stimulate immune cells.The resulting cascade of cytokines and mediators drives fibroblasts to differentiate into myofibroblasts,which secrete fibrillar collagens and transforming growth factor-β(TGF-β).Positive feedback networks then dysregulate processes that normally terminate healing processes.We propose two subtypes of arthrofibrosis occur:active arthrofibrosis and residual arthrofibrosis.In the latter the fibrogenic processes have resolved but the joint remains stiff.The best therapeutic approach for each subtype may differ significantly.Treatment typically involves surgery,however,a pharmacological approach to correct dysregulated cell signalling could be more effective.Recent research shows that myofibroblasts are capable of reversing differentiation,and understanding the mechanisms of pathogenesis and resolution will be essential for the development of cell-based treatments.Therapies with significant promise are currently available,with more in development,including those that inhibit TGF-βsignalling and epigenetic modifications.This review focuses on pathogenesis of sterile arthrofibrosis and therapeutic treatments.

Reperfusion after hypoxia-ischemia exacerbates brain injury with compensatory activation of the antiferroptosis system:based on a novel rat model

Hypoxic-ischemic encephalopathy,which predisposes to neonatal death and neurological sequelae,has a high morbidity,but there is still a lack of effective prevention and treatment in clinical practice.To better understand the pathophysiological mechanism underlying hypoxic-ischemic encephalopathy,in this study we compared hypoxic-ischemic reperfusion brain injury and simple hypoxic-ischemic brain injury in neonatal rats.First,based on the conventional RiceVannucci model of hypoxic-ischemic encephalopathy,we established a rat model of hypoxic-ischemic reperfusion brain injury by creating a common carotid artery muscle bridge.Then we performed tandem mass tag-based proteomic analysis to identify differentially expressed proteins between the hypoxic-ischemic reperfusion brain injury model and the conventional Rice-Vannucci model and found that the majority were mitochondrial proteins.We also performed transmission electron microscopy and found typical characteristics of ferroptosis,including mitochondrial shrinkage,ruptured mitochondrial membranes,and reduced or absent mitochondrial cristae.Further,both rat models showed high levels of glial fibrillary acidic protein and low levels of myelin basic protein,which are biological indicators of hypoxic-ischemic brain injury and indicate similar degrees of damage.Finally,we found that ferroptosis-related Ferritin(Fth1)and glutathione peroxidase 4 were expressed at higher levels in the brain tissue of rats with hypoxic-ischemic reperfusion brain injury than in rats with simple hypoxic-ischemic brain injury.Based on these results,it appears that the rat model of hypoxic-ischemic reperfusion brain injury is more closely related to the pathophysiology of clinical reperfusion.Reperfusion not only aggravates hypoxic-ischemic brain injury but also activates the anti-ferroptosis system.

Exosomes-the enigmatic regulators of bone homeostasis

Exosomes are a heterogeneous group of cell-derived membranous structures, which mediate crosstalk interaction between cells.Recent studies have revealed a close relationship between exosomes and bone homeostasis. It is suggested that bone cells can spontaneously secret exosomes containing proteins, lipids and nucleic acids, which then to regulate osteoclastogenesis and osteogenesis. However, the network of regulatory activities of exosomes in bone homeostasis as well as their therapeutic potential in bone injury remain largely unknown. This review will detail and discuss the characteristics of exosomes, the regulatory activities of exosomes in bone homeostasis as well as the clinical potential of exosomes in bone injury.

Human cytomegalovirus-encoded US28 may act as a tumor promoter in colorectal cancer

AIM: To assess human cytomegalovirus-encoded US28 gene function in colorectal cancer(CRC) pathogenesis.METHODS: Immunohistochemical analysis was performed to determine US28 expression in 103 CRC patient samples and 98 corresponding adjacent noncancerous samples. Patient data were compared by age, sex, tumor location, histological grade, Dukes' stage, and overall mean survival time. In addition, the US28 gene was transiently transfected into the CRC LOVO cell line, and cell proliferation was assessed using a cell counting kit-8 assay. Cell cycle analysis by flow cytometry and a cell invasion transwell assay were also carried out.RESULTS: US28 levels were clearly higher in CRC tissues(38.8%) than in adjacent noncancerous samples(7.1%)(P = 0.000). Interestingly, elevated US28 amounts in CRC tissues were significantly associated with histological grade, metastasis, Dukes' stage, and overall survival(all P < 0.05); meanwhile, US28 expression was not significantly correlated with age, sex or tumor location. In addition, multivariate Coxregression data revealed US28 level as an independent CRC prognostic marker(P = 0.000). LOVO cells successfully transfected with the US28 gene exhibited higher viability, greater chemotherapy resistance, accelerated cell cycle progression, and increased invasion ability.CONCLUSION: US28 expression is predictive of poor prognosis and may promote CRC.

Versatile subtypes of pericytes and their roles in spinal cord injury repair,bone development and repair

Vascular regeneration is a challenging topic in tissue repair. As one of the important components of the neurovascular unit(NVU),pericytes play an essential role in the maintenance of the vascular network of the spinal cord. To date, subtypes of pericytes have been identified by various markers, namely the PDGFR-β, Desmin, CD146, and NG2, each of which is involved with spinal cord injury(SCI) repair. In addition, pericytes may act as a stem cell source that is important for bone development and regeneration, whilst specific subtypes of pericyte could facilitate bone fracture and defect repair. One of the major challenges of pericyte biology is to determine the specific markers that would clearly distinguish the different subtypes of pericytes, and to develop efficient approaches to isolate and propagate pericytes. In this review, we discuss the biology and roles of pericytes, their markers for identification, and cell differentiation capacity with a focus on the potential application in the treatment of SCI and bone diseases in orthopedics.

The role of transporters in cancer redox homeostasis and cross-talk with nanomedicines

Tumor cell usually exhibits high levels of reactive oxygen species and adaptive antioxidant system due to the metabolic,genetic,and microenvironment-associated alterations.The altered redox homeostasis can promote tumor progression,development,and treatment resistance.Several membrane transporters are involved in the resetting redox homeostasis and play important roles in tumor progression.Therefore,targeting the involved transporters to disrupt the altered redox balance emerges as a viable strategy for cancer therapy.In addition,nanomedicines have drawn much attention in the past decades.Using nanomedicines to target or reset the redox homeostasis alone or combined with other therapies has brought convincing data in cancer treatment.In this review,we will introduce the altered redox balance in cancer metabolism and involved transporters,and highlight the recent advancements of redox-modulating nanomedicines for cancer treatment.

Bexarotene improves motor function after spinal cord injury in mice

Spinal cord injury is a challenge in orthopedics because it causes irreversible damage to the central nervous system.Therefore,early treatment to prevent lesion expansion is crucial for the management of patients with spinal cord injury.Bexarotene,a type of retinoid,exerts therapeutic effects on patients with cutaneous T-cell lymphoma and Parkinson's disease.Bexarotene has been proven to promote autophagy,but it has not been used in the treatment of spinal cord injury.To investigate the effects of bexarotene on spinal cord injury,we established a mouse model of T11–T12 spinal cord contusion and performed daily intraperitoneal injection of bexarotene for 5 consecutive days.We found that bexarotene effectively reduced the deposition of collagen and the number of pathological neurons in the injured spinal cord,increased the number of synapses of nerve cells,reduced oxidative stress,inhibited pyroptosis,promoted the recovery of motor function,and reduced death.Inhibition of autophagy with 3-methyladenine reversed the effects of bexarotene on spinal cord injury.Bexarotene enhanced the nuclear translocation of transcription factor E3,which further activated AMP-activated protein kinase-S-phase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signaling pathways.Intravenous injection of transcription factor E3 sh RNA or intraperitoneal injection of compound C,an AMP-activated protein kinase blocker,inhibited the effects of bexarotene.These findings suggest that bexarotene regulates nuclear translocation of transcription factor E3 through the AMP-activated protein kinase-Sphase kinase-associated protein 2-coactivator-associated arginine methyltransferase 1 and AMP-activated protein kinase-mammalian target of rapamycin signal pathways,promotes autophagy,decreases reactive oxygen species level,inhibits pyroptosis,and improves motor function after spinal cord injury.

Prevention of necrotizing enterocolitis in premature infants——an updated review

Necrotizing enterocolitis(NEC) is among the most common and devastating diseases encountered in premature infants, yet the true etiology continues to be poorly understood despite decades of research. Recently, gut bacterial dysbiosis has been proposed as a risk factor for the development of NEC. Based on this theory, several best clinical practices designed to reduce the risk of NEC have been proposed and/or implemented. This review summarizes the results of recent clinical trials and meta-analyses that support some of the existing clinical practices for reducing the risk of NEC in premature infants. It is evident that human milk feeding can reduce the incidence of NEC. While most of the studies demonstrated that probiotic supplementation can significantly reduce the incidence of NEC in premature infants, there are still some concerns regarding the quality, safety, optimal dosage, and treatment duration of probiotic preparations. Antibiotic prophylaxis does not reduce the incidence of NEC, and prolonged initial empirical use of antibiotics might in fact increase the risk of NEC for high-risk premature infants. Lastly, standardized feeding protocols are strongly recommended, both for prevention of postnatal growth restriction and NEC.

Functions and mechanisms of cytosolic phospholipase A_(2)in central nervous system trauma

Central nervous system(CNS)trauma,including traumatic brain injury and spinal cord injury,has a high rate of disability and mortality,and effective treatment is currently lacking.Previous studies have revealed that neural inflammation plays a vital role in CNS trauma.As the initial enzyme in neuroinflammation,cytosolic phospholipase A_(2)(cPLA2)can hydrolyze membranous phosphatides at the sn-2 position in a preferential way to release lysophospholipids andω3-polyunsaturated fatty acid dominated by arachidonic acid,thereby inducing secondary injuries.Although there is substantial fresh knowledge pertaining to cPLA2,in-depth comprehension of how cPLA2 participates in CNS trauma and the potential methods to amelio rate the clinical res ults after CNS trauma are still insufficient.The present review summarizes the latest understanding of how cPLA2 participates in CNS trauma,highlighting novel findings pertaining to how cPLA2 activation initiates the potential mechanisms specifically,neuroinflammation,lysosome membrane functions,and autophagy activity,that damage the CNS after trauma.Moreover,we focused on testing a variety of drugs capable of inhibiting cPLA2 or the upstream pathway,and we explored how those agents might be utilized as treatments to improve the results following CNS trauma.This review aimed to effectively understand the mechanism of cPLA2 activation and its role in the pathophysiological processes of CNS trauma and provide clarification and a new referential framework for future research.

Classification of four distinct osteoarthritis subtypes with a knee joint tissue transcriptome atlas

The limited molecular classifications and disease signatures of osteoarthritis(OA)impede the development of prediagnosis and targeted therapeutics for OA patients.To classify and understand the subtypes of OA,we collected three types of tissue including cartilage,subchondral bone,and synovium from multiple clinical centers and constructed an extensive transcriptome atlas of OA patients.By applying unsupervised clustering analysis to the cartilage transcriptome,OA patients were classified into four subtypes with distinct molecular signatures:a glycosaminoglycan metabolic disorder subtype(C1),a collagen metabolic disorder subtype(C2),an activated sensory neuron subtype(C3),and an inflammation subtype(C4).Through ligand-receptor crosstalk analysis of the three knee tissue types,we linked molecular functions with the clinical symptoms of different OA subtypes.For example,the Gene Ontology functional term of vasculature development was enriched in the subchondral bone-cartilage crosstalk of C2 and the cartilage-subchondral bone crosstalk of C4,which might lead to severe osteophytes in C2 patients and apparent joint space narrowing in C4 patients.Based on the marker genes of the four OA subtypes identified in this study,we modeled OA subtypes with two independent published RNA-seq datasets through random forest classification.The findings of this work contradicted traditional OA diagnosis by medical imaging and revealed distinct molecular subtypes in knee OA patients,which may allow for precise diagnosis and treatment of OA.

GW842166X Alleviates Osteoarthritis by Repressing LPS-mediated Chondrocyte Catabolism in Mice

Objective To explore the role and underlying mechanism of GW842166X on osteoarthritis and osteoarthritis-associated abnormal catabolism.Methods The extracted mouse chondrocytes were treated with GW842166X followed by lipopolysaccharide(LPS).The chondrocytes were divided into the control group,LPS group,LPS+50 nmol/L GW842166X group,and LPS+100 nmol/L GW842166X group.The cytotoxicity of GW842166X was tested using the CCK-8 assay.Western blot,RT-qPCR,and ELISA were applied to evaluate the expression of the inflammatory biomarkers in mouse chondrocytes.The expression of extracellular matrix molecules was detected by the Western blot,RT-qPCR,and immunofluorescence.Additionally,the activity of NF-κB was checked by the Western blot and immunofluorescence.The mouse Hulth models were generated to examine the in vivo effects of GW842166X on osteoarthritis.Hematoxylin and eosin staining,safranin O/fast green staining,and immunohistochemistry were applied to detect the histological changes.Results GW842166X below 200µmol/L had no cytotoxicity on the mouse chondrocytes.LPS-induced high expression of TGF-β1,IL-10,TNF-α,and IL-6 was significantly reduced by GW842166X.In addition,GW842166X upregulated the expression of aggrecan and collagen type III,which was downregulated after the LPS stimulation.The upregulated expression of ADAMTS-5 and MMP-13 by LPS stimulation was dropped in response to the GW842166X treatment.Furthermore,LPS decreased the IκBαexpression in the cytoplasm and increased the nuclear p65 expression.However,these changes were reversed by the GW842166X pretreatment.Moreover,the damages in the knees caused by the Hulth surgery in mice were restored by GW842166X.Conclusion GW842166X impeded the LPS-mediated catabolism in mouse chondrocytes,thereby inhibiting the progression of osteoarthritis.

Alantolactone-loaded chitosan/hyaluronic acid nanoparticles suppress psoriasis by deactivating STAT3 pathway and restricting immune cell recruitment

Psoriasis is a common chronic immune-mediated skin disease characterized by hyperproliferation and aberrant differentiation of keratinocytes and massive infiltration of inflammatory immune cells.Recent studies showed that Signal Transducer and Activator of Transcription 3(STAT3),which plays an important role in cell survival,proliferation,differentiation,angiogenesis,and immune responses,is constitutively activated in epidermal keratinocytes of human psoriatic skin lesions.In addition,STAT3 promotes the differentiation and expansion of T cells and facilitates cytokine production,thereby exacerbating the condition of psoriasis.Alantolactone(ALT)is a sesquiterpene lactone compound that could selectively suppress STAT3 activation,but its effectiveness and application in psoriasis treatment have not been determined.In this study,we developed ALT loaded chitosan/hyaluronic acid nanoparticles(CHALT),and investigated its therapeutic potential for psoriasis therapy.CHALT effectively abrogated the hyperproliferation by inducing ROS-mediated apoptosis with loss of mitochondrialmembrane potential,and also inhibited IL-6-induced STAT3 signaling activation and inflammatory reaction in HaCaT cell line.In an Imiquimod(IMQ)-induced psoriasis model,the topical treatment of psoriasis lesions with CHALT effectively attenuated the STAT3 hyperactivation within keratinocytes and ameliorated the symptoms of psoriasis.In addition,it was found that CHALT restricted the recruitment of immune cells.These results indicated that ALT-based nanoformulation CHALT holds great potential for psoriasis therapy.

Noteworthy effects of a long-pulse Alexandrite laser for treatment of high-risk infantile hemangioma: A case report and literature review

BACKGROUND We have previously proved that treatment of thick/deep infantile hemangiomas (IHs) with a long-pulse Alexandrite laser was clinically effective and safe. This article aims to investigate the efficiency of long-pulse Alexandrite laser use in treating thick and high-risk IHs located in particular anatomic areas and provides some new data on this issue. CASE SUMMARY A two-month-old girl with a thick and high-risk IH covering most of the right labia majora was examined in this study. The infant received four treatment sessions at 4- to 6-wk intervals with a long-pulse Alexandrite laser with settings as follows: 3 ms pulse duration, 8 mm spot size, 45 to 50 J/cm2 fluences, and dynamic cooling device (DCD) spray duration of 90 ms with a delay of 80 ms. Following each of the four treatment sessions, the IH showed a remarkable reduction in thickness and size without any sign of relapse. Ten months after the last treatment, the IH had completely regressed without adverse effects. During the laser treatment, no severe side effects were observed;blistering occurred only immediately after treatment and then scabbed over the next day, gradually improving in the following days. CONCLUSION Long-pulse Alexandrite laser treatment may be considered one of the first-line noninvasive therapeutic options for the treatment of thick IH.

Concentrations of Polybrominated Diphenyl Ethers in Maternal Blood,Placental Size,and Risk for Fetal Growth Restriction:A Nested Case-control Study

Objective To explore the effects of prenatal exposure to polybrominated diphenyl ethers(PBDEs)on placental size and birth outcomes.Methods Based on the perspective Wenzhou Birth Cohort,this nested case-control study included 101 fetal growth restriction(FGR)and 101 healthy newborns.Maternal serum samples were collected during the third trimester and measured for PBDEs by gas chromatography tandem mass spectrometry.The basic information of mother-newborn pairs was collected from questionnaires,whereas the placental size and birth outcomes of newborns were obtained from hospital records.Results A total of 19 brominated diphenyle ether(BDE)congeners were detected in maternal serum samples.Higher concentrations of BDE-207,-208,-209,and∑19PBDEs were detected in FGR cases than in controls.Increased BDE-207,-208,-209,and∑19PBDEs levels in maternal serum were related to decreased placental length,breadth,surface area,birth weight,birth length,gestational age,and Quetelet index of newborns.After adjusting for confounders,BDE-207 and∑19PBDE concentrations in maternal serum were significantly associated with an increased risk of FGR.Conclusion A negative association was found between PBDE levels in maternal serum and placental size and birth outcomes.Prenatal PBDE exposure may be associated with elevated risk of the incidence of FGR birth.