Small extracellular vesicles derived from cerebral endothelial cells with elevated microRNA 27a promote ischemic stroke recovery

Axonal remodeling is a critical aspect of ischemic brain repair processes and contributes to spontaneous functional recovery.Our previous in vitro study demonstrated that exosomes/small extracellular vesicles(sEVs)isolated from cerebral endothelial cells(CEC-sEVs)of ischemic brain promote axonal growth of embryonic cortical neurons and that microRNA 27a(miR-27a)is an elevated miRNA in ischemic CEC-sEVs.In the present study,we investigated whether normal CEC-sEVs engineered to enrich their levels of miR-27a(27a-sEVs)further enhance axonal growth and improve neurological outcomes after ischemic stroke when compared with treatment with non-engineered CEC-sEVs.27a-sEVs were isolated from the conditioned medium of healthy mouse CECs transfected with a lentiviral miR-27a expression vector.Small EVs isolated from CECs transfected with a scramble vector(Scra-sEVs)were used as a control.Adult male mice were subjected to permanent middle cerebral artery occlusion and then were randomly treated with 27a-sEVs or Scra-sEVs.An array of behavior assays was used to measure neurological function.Compared with treatment of ischemic stroke with Scra-sEVs,treatment with 27a-sEVs significantly augmented axons and spines in the peri-infarct zone and in the corticospinal tract of the spinal grey matter of the denervated side,and significantly improved neurological outcomes.In vitro studies demonstrated that CEC-sEVs carrying reduced miR-27a abolished 27a-sEV-augmented axonal growth.Ultrastructural analysis revealed that 27a-sEVs systemically administered preferentially localized to the pre-synaptic active zone,while quantitative reverse transcription-polymerase chain reaction and Western Blot analysis showed elevated miR-27a,and reduced axonal inhibitory proteins Semaphorin 6A and Ras Homolog Family Member A in the peri-infarct zone.Blockage of the Clathrin-dependent endocytosis pathway substantially reduced neuronal internalization of 27a-sEVs.Our data provide evidence that 27a-sEVs have a therapeutic effect on stroke recovery by promoting axonal remodeling and improving neurological outcomes.Our findings also suggest that suppression of axonal inhibitory proteins such as Semaphorin 6A may contribute to the beneficial effect of 27a-sEVs on axonal remodeling.

Study on crustal thickness and the prediction of prolific depressions:the Bohai Basin as an example

The deep crustal structure is closely related to oil and gas reserves.Predicting the oil and gas enrichment of depressions based on the Moho depth and crustal thickness is a promising research topic with significant implications for guiding exploration in petroliferous basins.In this study,seismic data were used as a constraint on the use of satellite gravity anomaly inversion to obtain the distribution of Moho depth and crustal thickness in the Bohai Basin.Stretching factors were calculated to analyze the differential distribution of deep crustal structural activity.Four indicators,including the minimum Moho depth,minimum crustal thickness,sum of Moho stretching factors,and sum of crustal stretching factors,were selected.Principal component analysis was applied to reduce the dimensionality of the multi-indicator system and obtain an oil and gas enrichment score for quantitative prediction of favorable prolific depressions.The deviation between the inverted Moho depth and seismic constraints was small;thus,the data effectively reflect the variations in the characteristics of each depression.The analysis revealed significant statistical features related to the minimum Moho depth/crustal thickness and the sum of Moho/crustal stretching factors associated with prolific depressions.Based on the oil and gas enrichment score,the depressions were classified into four categories related to their different deep crustal structural characteristics.Highly active ClassⅠ,ClassⅡ,and ClassⅢdepressions are predicted to be favorable prolific depressions.This study expands the research on quantitatively predicting favorable prolific depressions in the Bohai Basin using the deep crustal structure and can contribute to reducing production costs and improving exploration efficiency in future explorations.

Structural characteristics and tectonic division of the Zambezi Delta basin in the offshore East Africa:evidences from gravity and seismic data

The Zambezi Delta basin is a passive marginal basin located on the East African coast that has good oil and gas exploration potential.Due to the special geological evolutionary background of the Beira High in the Zambezi Delta basin,it has a low gravity anomaly,and the existing seismic survey lines do not cover the whole basin;therefore,it is difficult to interpret the structural characteristics of the whole basin based solely on gravity or seismic data.Based on satellite altimetry gravity anomaly data,this study infers the distribution characteristics of faults in the Zambezi Delta basin by using the normalized vertical derivative of the total horizontal derivative(NVDR-THDR)technique.Then,constrained by seismic data,the gravity anomaly at the Moho interface is extracted by using the fast forward method of the double-interface model of the gravity anomaly,and this anomaly is then removed from the Bouguer gravity anomaly to obtain the sedimentary layer gravity anomaly.The thickness of the sedimentary strata is obtained by inversing the sedimentary basement depth of the whole basin.Then,uplifts and depressions are divided based on a sedimentary layer thickness of 3 km.This research demonstrates that the Zambezi Delta basin mainly features nearly SN-trending and NE-trending faults and that these faults exhibit east-west partitioning.The nearly SN-trending strike-slip faults controlled the sedimentary development of the basin,and the NE-trending tensile faults may have acted as migration channels for oil,gas and magma.The“overcompensation”effect of the Moho interface gravity anomaly on the gravity anomaly of the sedimentary layer is caused by the depression of the Moho interface beneath the Beira High,which results in a low gravity anomaly value for the Beira High.The pattern of uplifts and depressions trends NE and has the structural characteristics of east-west blocks.

Influence of lithospheric thickness distribution on oil and gas basins,China seas and adjacent areas

The distribution of oil and gas resources is intricately connected to the underlying structure of the lithosphere.Therefore,investigating the characteristics of lithospheric thickness and its correlation with oil and gas basins is highly important.This research utilizes recently enhanced geological–geophysical data,including topographic,geoid,rock layer thickness,variable rock layer density,and interface depth data.Employing the principles of lithospheric isostasy and heat conduction,we compute the laterally varying lithospheric thickness in the China seas and adjacent areas.From these results,two pivotal parameters for different types of oil and gas basins were statistically analyzed:the minimum lithospheric thickness and the relative fluctuation in lithospheric thickness.A semiquantitative analysis was used to explore the connection between these parameters and the hydrocarbon abundance within the oil and gas basins.This study unveils distinct variations in lithospheric thickness among basins,with oil and gas rich basins exhibiting a thicker lithosphere in the superimposed basins of central China and a thinner lithosphere in the rift basins of eastern China.Notably,the relative fluctuations in lithospheric thickness in basins demonstrate significant disparities:basins rich in oil and gas often exhibit greater thickness fluctuations.Additionally,in the offshore basins of China,a conspicuous negative linear correlation is observed between the minimum lithospheric thickness and the relative fluctuation in lithospheric thickness.This study posits that deep-seated thermal upwelling results in lithospheric undulations and extensional thinning in oil and gas basins.Concurrently,sustained deep-seated heat influences sedimentary materials in basins,creating favorable conditions for oil and gas generation.The insights derived from this study contribute to a quantitative understanding of the intricate relationships between deep lithospheric structures and oil and gas basins.These findings provide valuable guidance for future oil and gas exploration in the studied areas.

Potential beneficial effects of butyrate in intestinal and extraintestinal diseases

The multiple beneficial effects on human health of the short-chain fatty acid butyrate,synthesized from nonabsorbed carbohydrate by colonic microbiota,are well documented.At the intestinal level,butyrate plays a regulatory role on the transepithelial fluid transport,ameliorates mucosal inflammation and oxidative status,reinforces the epithelial defense barrier,and modulates visceral sensitivity and intestinal motility.In addition,a growing number of studies have stressed the role of butyrate in the prevention and inhibition of colorectal cancer.At the extraintestinal level,butyrate exerts potentially useful effects on many conditions,including hemoglobinopathies,genetic metabolic diseases,hypercholesterolemia,insulin resistance,and ischemic stroke.The mechanisms of action of butyrate are different;many of these are related to its potent regulatory effects on gene expression.These data suggest a wide spectrum of positive effects exerted by butyrate,with a high potential for a therapeutic use in human medicine.

Predictive factors for anastomotic leakage after laparoscopic colorectal surgery

Every colorectal surgeon during his or her career is faced with anastomotic leakage(AL); one of the most dreaded complications following any type of gastrointestinal anastomosis due to increased risk of morbidity, mortality, overall impact on functional and oncologic outcome and drainage on hospital resources. In order to understand and give an overview of the AL risk factors in laparoscopic colorectal surgery, we carried out a careful review of the existing literature on this topic and found several different definitions of AL which leads us to believe that the lack of a consensual, standard definition can partly explain the considerable variations in reported rates of AL in clinical studies. Colorectal leak rates have been found to vary depending on the anatomic location of the anastomosis with reported incidence rates ranging from 0 to 20%, while the laparoscopic approach to colorectal resections has not yet been associated with a significant reduction in AL incidence. As well, numerous risk factors, though identified, lack unanimous recognition amongst researchers. For example, the majority of papers describe the risk factors for left-sided anastomosis, the principal risk being male sex and lower anastomosis, while little data exists defining AL risk factors in a right colectomy. Also, gut microbioma is gaining an emerging role as potential risk factor for leakage.

Minimally invasive treatment of cholecysto-choledocal lithiasis:The point of view of the surgical endoscopist

The rate of choledocholithiasis in patients with symptomatic cholelithiasis is estimated to be approximately 10%-33%,depending on the patient's age.Development of Endoscopic Retrograde Cholangiopancreatography and Laparoscopic Surgery and improvement of diagnostic procedures have influenced new approaches to the management of common bile duct stones in association with gallstones.At present available minimally-invasive treatments of cholecysto-choledocal lithiasis include:single-stage laparoscopic treatment,perioperative endoscopic treatment and endoscopic treatment alone.Published data evidence that,associated endoscopic-laparoscopic approach necessitates increased number of procedures per patient while single-stage laparoscopic treatment is associated with a shorter hospital stay.However,current data does not suggest clear superiority of any one approach with regard to success,mortality,morbidity and cost-effectiveness.Considering the variety of therapeutic options available for management,a critical appraisal and decision-making is required.endoscopic retrograde cholangiopancreatography/EST should be adopted on a selective basis,i.e.,in patients with acute obstructive suppurative cholangitis,severe biliary pancreatitis,ampullary stone impaction or severe comorbidity.In a setting where all facilities are available,decision in the selection of the therapeutic option depends on the patients,the number and size of choledocholithiasis stones,the anatomy of the cystic duct and common bile duct,the surgical history of patients and local expertise.

Endoscopic papillectomy: Indications, techniques, and results

Endoscopic papillectomy (EP) is currently accepted as a viable alternative therapy to surgery in sporadic ampullary adenoma and has been reported to have high success and low recurrence rates. At present, the indications for EP are not yet fully established. The accepted criteria for EP include size (up to 5 cm), no evidence of intraductal growth, and no evidence of malignancy on endoscopic findings (ulceration, friability, and spontaneous bleeding). Endoscopic ultrasound (EUS) is the imaging modality of choice for local T staging in ampullary neoplasms. Data reported in the literature have revealed that linear EUS is superior to helical computed tomography in the preoperative assessment of tumor size, detection of regional nodal metastases and detection of major vascular invasion. Endoscopic ampullectomy is performed using a standard duodenoscope in a similar manner to snare polypectomy of a mucosal lesion. There is no standardization of the equipment or technique and broad EP methods are described. Endoscopic ampullectomy is considered a ‘‘high-risk’’ procedure due to complications. Complications of endoscopic papillectomy can be classified as early (pancreatitis, bleeding, perforation, and cholangitis) and late (papillary stenosis) complications. The appropriate use of stenting after ampullectomy may prevent post-procedural pancreatitis and papillary stenosis. Tumor recurrence of benign lesions occurs in up to 20% of patients and depends on tumor size, final histology, presence of intraductal tumor, coexisting familial adenomatous polyposis (FAP), and the expertise of the endoscopist. Recurrent lesions are usually benign and most can be retreated endoscopically.

Hepatitis B in pregnancy

Chronic hepatitis B virus (HBV) infection affects about 350 million individuals worldwide. Management of HBV infection in pregnancy is difficult because of several peculiar and somewhat controversial aspects. The aim of the present review is to provide a tool that may help physicians to correctly manage HBV infection in pregnancy. This review focuses on (1) the effect of pregnancy on HBV infection and of HBV infection on pregnancy; (2) the potential viral transmission from mother to newborn despite at-birth prophylaxis with immunoglobulin and vaccine; (3) possible prevention of mother-to-child transmission through antiviral drugs, the type of antiviral drug to use considering their efficacy and potential teratogenic effect, and the timing of their administration and discontinuation; and (4) the evidence for the use of elective caesarean section vs vaginal delivery and the possibility of breastfeeding.

Confocal laser endomicroscopy in the “in vivo” histological diagnosis of the gastrointestinal tract

Recent technological advances in miniaturization have allowed for a confocal scanning microscope to be integrated into a conventional flexible endoscope,or into trans-endoscopic probes,a technique now known as confocal endomicroscopy or confocal laser endomicroscopy.This newly-developed technology has enabled endoscopists to collect real-time in vivo histological images or "virtual biopsies" of the gastrointestinal mucosa during endoscopy,and has stimulated significant interest in the application of this technique in clinical gastroenterology.This review aims to evaluate the current data on the technical aspects and the utility of this new technology in clinical gastroenterology and its potential impact in the future,particularly in the screening or surveillance of gastrointestinal neoplasia.

Cardiovascular and metabolic effects of Berberine

Berberine(BBR) is a natural alkaloid isolated from the Coptis Chinensis.While this plant has been used in Ay-urvedic and Chinese medicine for more than 2500 years,interest in its effects in metabolic and cardiovascular disease has been growing in the Western world in the last decade.Many papers have been published in these years reporting beneficial effects in carbohydrate and lip-id metabolism,endothelial function and the cardiovascu-lar system.In this review,we report a detailed analysis of the scientific literature regarding this topic,describing the effects and the underlying mechanisms of BBR on carbohydrate and lipid metabolism,endothelial function and the cardiovascular system.

Current concepts and future strategies in the antimicrobial therapy of emerging Gram-positive spontaneous bacterial peritonitis

Spontaneous bacterial peritonitis(SBP) is the most common infection in end-stage liver disease patients.SBP is defined as an ascitic fluid infection with a polymorphonuclear leucocyte count ≥ 250/mm^3 without an evident intra-abdominal surgically treatable source.Several mechanisms contribute to SBP occurrence,including translocation of gut bacteria and their products,reduced intestinal motility provoking bacterial overgrowth,alteration of the gut's barrier function and local immune responses.Historically,Gram-negative enteric bacteria have been the main causative agents of SBP,thereby guiding the empirical therapeutic choice.However,over the last decade,a worryingly increasing prevalence of Gram-positive and multi-drug resistant(MDR) SBP has been seen.Recently,the microbiological spectrum of SBP seems to have changed in Europe due to a high prevalence of Gram-positive bacteria(48%-62%).The overall proportion of MDR bacteria is up to 22%-73% of cases.Consequently,empirical therapy based on thirdgeneration cephalosporins or amoxicillin/clavulanic acid,can no longer be considered the standard of care,as these drugs are associated with poor outcomes.Theaim of this review is to describe,with an epidemiological focus,the evidence behind this rise in Gram-positive and MDR SBP from 2000 to present,and illustrate potential targeted therapeutic strategies.An appropriate treatment protocol should include daptomycin plus ceftaroline and meropenem,with prompt stepdown to a narrower spectrum when cultures and sensitivity data are available in order to reduce both cost and potential antibiotic resistance development.

Role of brain-derived neurotrophic factor during the regenerative response after traumatic brain injury in adult zebrafish

Several mammalian animal models of traumatic brain injury have been used, mostly rodents. However, reparative mechanisms in mammalian brain are very limited, and newly formed neurons do not survive for long time. The brain of adult zebrafish, a teleost fish widely used as vertebrate model, possesses high regenerative properties after injury due to the presence of numerous stem cells niches. The ventricular lining of the zebrafish dorsal telencephalon is the most studied neuronal stem cell niche because its dorso-lateral zone is considered the equivalent to the hippocampus of mammals which contains one of the two constitutive neurogenic niches of mammals. To mimic TBI, stab wound in the dorso-lateral telencephalon of zebrafish was used in studies devoted to fish regenerative properties. Brain-derived neurotrophic factor, which is known to play key roles in the repair process after traumatic brain lesions, persists around the lesioned area of injured telencephalon of adult zebrafish. These results are extensively compared to reparative processes in rodent brain. Considering the complete repair of the damaged area in fish, it could be tempting to consider brain-derived neurotrophic factor as a factor contributing to create a permissive environment that enables the establishment of new neuronal population in damaged brain.

emerging role of the β-catenin-PPARγ axis in the pathogenesis of colorectal cancer

Multiple lines of evidence indicate that Wnt/β-catenin signaling plays a fundamental role in colorectal cancer (CRC) initiation and progression. Recent genome-wide data have confirmed that in CRC this pathway is one of the most frequently modified by genetic or epigenetic alterations affecting almost 90% of Wnt/β-catenin gene members. A major challenge is thus learning how the corrupted coordination of this pathway is tied to other signalings to enhance cell growth. Peroxisome proliferator activated receptor γ (PPARγ) is emerging as a growth-limiting and differentiation-promoting factor. In tumorigenesis it exerts a tumor suppressor role and is potentially linked with the Wnt/β-catenin pathway. Based on these results, the identification of new selective PPARγ modulators with inhibitory effects on the Wnt/β-catenin pathway is becoming an interesting perspective. Should, in fact, these molecules display such properties, new research avenues would be opened aimed at developing new molecular targeted drugs. Herein, we review the basic principles and present new hypotheses underlying the crosstalk between Wnt/β-catenin and PPARγ signaling. Furthermore, we discuss the advances in our understanding as to how their altered regulation can culminate in colon cancer and the efforts aimed at designing novel PPARγ agonists endowed with Wnt/β-catenin inhibitory effects to be used as therapeutic and/or preventive agents.

S100B protein in the gut:The evidence for enteroglial-sustained intestinal inflammation

Glial cells in the gut represent the morphological and functional equivalent of astrocytes and microglia in the central nervous system （CNS）. In recent years, the role of enteric glial cells （EGCs） has extended from that of simple nutritive support for enteric neurons to that of being pivotal participants in the regulation of inflammatory events in the gut. Similar to the CNS astrocytes, the EGCs physiologically express the SIOOB protein that exerts either trophic or toxic effects depending on its concentration in the extracellular milieu. In the CNS, SIOOB overexpression is responsible for the initiation of a gliotic reaction by the release of pro-inflammatory mediators, which may have a deleterious effect on neighboring cells. SlOOB-mediated pro-inflammatory effects are not limited to the brain： SIOOB overexpression is associated with the onset and maintenance of inflammation in the human gut too. In this review we describe the major features of EGCs and SIOOB protein occurring in intestinal inflammation deriving from such.

Cerebellum and neurodegenerative diseases:Beyond conventional magnetic resonance imaging

The cerebellum plays a key role in movement control and in cognition and cerebellar involvement is described in several neurodegenerative diseases.While conventional magnetic resonance imaging(MRI) is widely used for brain and cerebellar morphologic evaluation,advanced MRI techniques allow the investigation of cerebellar microstructural and functional characteristics.Volumetry,voxel-based morphometry,diffusion MRI based fiber tractography,resting state and task related functional MRI,perfusion,and proton MR spectroscopy are among the most common techniques applied to the study of cerebellum.In the present review,after providing a brief description of each technique's advantages and limitations,we focus on their application to the study of cerebellar injury in major neurodegenerative diseases,such as multiple sclerosis,Parkinson's and Alzheimer's disease and hereditary ataxia.A brief introduction to the pathological substrate of cerebellar involvement is provided for each disease,followed by the review of MRI studies exploring structural and functional cerebellar abnormalities and by a discussion of the clinical relevance of MRI measures of cerebellar damage in terms of both clinical status and cognitive performance.

Air quality nearby road traffic tunnel portals: BTEX monitoring

A monitoring campaign of BTEX （benzene, toluene, ethylbenzene, o- m- and p-xylene） was carried out nearby two tunnel portals in the urban area of Naples with the aim to verify air quality in this kind of urban sites. Sampling was carried out using the active adsorption technique. Sampling time was 1 h. Ambient temperature and traffic flow measurements were carried out during each sampling operation. The results indicate that average benzene concentrations at both sites exceed the limit value of 10 μg/Nm^3 established by the European Community （EC） （Dir. 2000/69）. Concentration levels of other BTEX are relatively high as well. A correlation between BTEX concentration and two wheeler vehicle flow was observed.

Endoscopic approach to malignant strictures at the hepatic hilum

Hilar tumors have proven to be a challenge to treat and manage because of their poor sensitivity to conventional therapies and our inability to prevent or to detect early tumor formation. Endoscopic stent drainage has been proposed as an alternative to biliary-enteric bypass surgery and percutaneous drainage to palliate malignant biliary obstruction. Prosthetic palliation of patients with malignant hilar stenoses poses particular difficulties, especially in advanced lesions （type Ⅱ lesions or higher）. The risk of cholangitis after contrast injection into the biliary tree in cases where incomplete drainage is achieved is well known. The success rate of plastic stent insertion is around 80% in patients with proximal tumors. Relief of symptoms can be achieved in nearly all patients successfully stented.

Vertical hepatitis C virus transmission:Main questions and answers

Hepatitis C virus(HCV) affects about 3% of the world's population and peaks in subjects aged over 40 years. Its prevalence in pregnant women is low(1%-2%) in most western countries but drastically increases in women in developing countries or with high risk behav-iors for blood-transmitted infections. Here we review clinical, prognostic and therapeutic aspects of HCV in-fection in pregnant women and their offspring infected through vertical transmission. Pregnancy-related im-mune weakness does not seem to affect the course of acute hepatitis C but can affect the progression of chronic hepatitis C. In fact, postpartum immune res-toration can exacerbate hepatic inflammation, thereby worsening the liver disease, particularly in patients with liver cirrhosis. HCV infection increases the risk of gestational diabetes in patients with excessive weight gain, premature rupture of membrane and caesarean delivery. Only 3%-5% of infants born to HCV-positive mothers have been infected by intrauterine or perinatal transmission. Maternal viral load, human immunode-ficiency virus coinfection, prolonged rupture of mem-branes, fetal exposure to maternal infected blood con-sequent to vaginal or perineal lacerations and invasive monitoring of fetus increase the risk of viral transmis-sion. Cesarean delivery and breastfeeding increases the transmission risk in HCV/human immunodeficiency virus coinfected women. The consensus is not to offer antivi-ral therapy to HCV-infected pregnant women because it is based on ribavirin(pregnancy category X) because of its embryocidal and teratogenic effects in animal spe-cies. In vertically infected children, chronic C hepatitis is often associated with minimal or mild liver disease and progression to liver cirrhosis and hepatocarcinoma is lower than in adults. Infected children may be treated after the second year of life, given the adverse effects of current antiviral agents.

Helicobacter pylori gamma-glutamyl transpeptidase and its pathogenic role

Helicobacter pylori(H.pylori)gamma-glutamyl transpeptidase(GGT)is a bacterial virulence factor that converts glutamine into glutamate and ammonia,and converts glutathione into glutamate and cysteinylglycine.H.pylori GGT causes glutamine and glutathione consumption in the host cells,ammonia production and reactive oxygen species generation.These products induce cell-cycle arrest,apoptosis,and necrosis in gastric epithelial cells.H.pylori GGT may also inhibit apoptosis and induce gastric epithelial cell proliferation through the induction of cyclooxygenase-2,epidermal growth factor-related peptides,inducible nitric oxide synthase and interleukin-8.H.pylori GGT induces immune tolerance through the inhibition of T cell-mediated immunity and dendritic cell differentiation.The effect of GGT on H.pylori colonization and gastric persistence are also discussed.