Kinetics and Modeling of Chemical Leaching of Sphalerite Concentrate Using Ferric Iron in a Redox-controlled Reactor

This work presents a study for chemical leaching of sphalerite concentrate under various constant Fe3+ concentrations and redox potential conditions. The effects of Fe3+ concentration and redox potential on chemical leaching of sphalerite were investigated. The shrinking core model was applied to analyze the experimental results. It was found that both the Fe3+ concentration and the redox potential controlled the chemical leaching rate of sphalerite. A new kinetic model was developed, in which the chemical leaching rate of sphalerite was proportional to Fe3+ concentration and Fe3+ /Fe2+ ratio. All the model parameters were evaluated from the experimental data. The model predictions fit well with the experimental observed values.

Longitudinal analysis of inflammation and microbiota dynamics in a model of mild chronic dextran sulfate sodium-induced colitis in mice

AIM: To characterize longitudinally the inflammation and the gut microbiota dynamics in a mouse model of dextran sulfate sodium (DSS)-induced colitis.

Potential role of the gut microbiota in synthetic torpor and therapeutic hypothermia

Therapeutic hypothermia is today used in several clinical settings, among them the gut related diseases that are influenced by ischemia/reperfusion injury. This perspective paved the way to the study of hibernation physiology, in natural hibernators, highlighting an unexpected importance of the gut microbial ecosystem in hibernation and torpor. In natural hibernators, intestinal microbes adaptively reorganize their structural configuration during torpor, and maintain a mutualistic configuration regardless of long periods of fasting and cold temperatures. This allows the gut microbiome to provide the host with metabolites, which are essential to keep the host immunological and metabolic homeostasis during hibernation. The emerging role of the gut microbiota in the hibernation process suggests the importance of maintaining a mutualistic gut microbiota configuration in the application of therapeutic hypothermia as well as in the development of new strategy such as the use of synthetic torpor in humans. The possible utilization of tailored probiotics to mold the gut ecosystem during therapeutic hypothermia can also be taken into consideration as new therapeutic strategy.

Correlation of molecular alterations with pathological features in hepatocellular carcinoma:Literature review and experience of an Italian center

Hepatocellular carcinoma(HCC)represents the primary carcinoma of the liver and the fourth leading cause of cancer-related deaths.The World Health Organization estimates an increase in cases in the coming years.The risk factors of HCC are multiple,and the incidence in different countries is closely related to the different risk factors to which the population is exposed.The molecular mechanisms that drive HCC tumorigenesis are extremely complex,but understanding this multistep process is essential for the identification of diagnostic,prognostic,and therapeutic markers.The development of multigenic nextgeneration sequencing panels through the parallel analysis of multiple markers can provide a landscape of the genomic status of the tumor.Considering the literature and our preliminary data based on 36 HCCs,the most frequently altered genes in HCCs are TERT,CTNNB1,and TP53.Over the years,many groups have attempted to classify HCCs on a molecular basis,but a univocal classification has never been achieved.Nevertheless,statistically significant correlations have been found in HCCs between the molecular signature and morphologic features,and this leads us to think that it would be desirable to integrate the approach between anatomic pathology and molecular laboratories.

Inflammation and colorectal cancer, when microbiota-host mutualism breaks

Structural changes in the gut microbial community have been shown to accompany the progressive development of colorectal cancer.In this review we discuss recent hypotheses on the mechanisms involved in the bacteria-mediated carcinogenesis,as well as the triggering factors favoring the shift of the gut microbiota from a mutualistic to a pro-carcinogenic configuration.The possible role of inflammation,bacterial toxins and toxic microbiota metabolites in colorectal cancer onset is specifically discussed.On the other hand,the strategic role of inflammation as the keystone factor in driving microbiota to become carcinogenic is suggested.As a common outcome of different environmental and endogenous triggers,such as diet,aging,pathogen infection or genetic predisposition,inflammation can compromise the microbiota-host mutualism,forcing the increase of pathobionts at the expense of health-promoting groups,and allowing the microbiota to acquire an overall pro-inflammatory configuration.Consolidating inflammation in the gut,and favoring the bloom of toxigenic bacterial drivers,these changes in the gut microbial ecosystem have been suggested as pivotal in promoting carcinogenesis.In this context,it will become of primary importance to implement dietary or probiotics-based interventions aimed at preserving the microbiota-host mutualism along aging,counteracting deviations that favor a pro-carcinogenic microbiota asset.

role of microRNAs in the main molecular pathways of hepatocellular carcinoma

Hepatocellular carcinoma(HCC) is the most common primary liver malignant neoplasia. HCC is characterized by a poor prognosis. The need to find new molecular markers for its diagnosis and prognosis has led to a progressive increase in the number of scientific studies on this topic. MicroRNAs(miRNAs) are small noncoding RNA that play a role in almost all main cellular pathways. miRNAs are involved in the regulation of expression of the major tumor-related genes in carcinogenesis, acting as oncogenes or tumor suppressor genes. The aim of this review was to identify papers published in 2017 investigating the role of miRNAs in HCC tumorigenesis. miRNAs were classified according to their role in the main molecular pathways involved in HCC tumorigenesis:(1) m TOR;(2) Wnt;(3) JAK/STAT;(4) apoptosis; and(5) MAPK. The role of miRNAs in prognosis/response prediction was taken into consideration. Bearing in mind that the analysis of miRNAs in serum and other body fluids would be crucial for clinical management, the role of circulating miRNAs in HCC patients was also investigated. The most represented mi RNA-regulated pathway in HCC is m TOR, but apoptosis, Wnt, JAK/STAT or MAPK pathways are also influenced by mi RNA expression levels. These miRNAs could thus be used in clinical practice as diagnostic, prognostic or therapeutic targets for HCC treatment.

Paradoxical relationship between proton pump inhibitors and COVID-19: A systematic review and meta-analysis

BACKGROUND The proton pump inhibitors(PPIs),used to reduce gastric acid secretion,represent one of the most widely used pharmaceutical classes in the world.Their consumption as a risk factor for the evolution of severe forms of severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)infection has been investigated as well as the mortality of these patients.These risks also appear to be linked to the duration and the dosage.On the other hand,several studies have emerged with regard to the protective or therapeutic effects of these drugs.More and more evidence underlines the immunomodulatory and anti-fibrotic role of PPIs.In addition,their ability to alkalize the contents of endosomes and lysosomes serves as an obstacle to the entry of the virus into the host cells.AIM To identify studies on the relationship between the intake of PPIs and coronavirus disease 2019(COVID-19)in patients affected by SARS-CoV-2 infection,with the main objective of evaluating the outcomes related to severity and mortality.METHODS A literature review was performed in November 2020.The MEDLINE/PubMed,Cochrane Library,EMBASE and Google Scholar databases were searched for all relevant articles published in English on this topic.The search terms were identified by means of controlled vocabularies,such as the National Library of Medicine’s MESH(Medical Subject Headings)and keywords.The MESH terms and keywords used were as follows:“COVID-19”,“proton pump inhibitors”,“PPIs”,“SARS-CoV-2”,“outcomes”,“severity”and“mortality”.The inclusion criteria regarding the studies considered in our analysis were:meta-analysis,casecontrol,hospital-based case-control,population-based case-control,retrospective studies,online survey,as well as cohort-studies,while articles not published as full reports,such as conference abstracts,case reports and editorials were excluded.We tried to summarize and pool all the data if available.RESULTS A total of 9 studies were found that described the use of PPIs,of which only 5 clearly reported the severity and mortality data in SARS-CoV-2 patients.Our pooled incidence analysis of severe events did not differ between patients with and without PPIs(odds ratio 1.65,95%confidence interval:0.62-4.35)(P=0.314),or for mortality(odds ratio 1.77,95%confidence interval:0.62-5.03)(P=0.286).CONCLUSION Detailed and larger case studies are needed to accurately understand the role of PPIs in this viral infection.

Neuroprotection and neuroregeneration:roles for the white matter

Efficient strategies for neuroprotection and repair are still an unmet medical need for neurodegenerative diseases and lesions of the central nervous system.Over the last few decades,a great deal of attention has been focused on white matter as a potential therapeutic target,mainly due to the discovery of the oligodendrocyte precursor cells in the adult central nervous system,a cell type able to fully repair myelin damage,and to the development of advanced imaging techniques to visualize and measure white matter lesions.The combination of these two events has greatly increased the body of research into white matter alte rations in central nervous system lesions and neurodegenerative diseases and has identified the oligodendrocyte precursor cell as a putative target for white matter lesion repair,thus indirectly contributing to neuroprotection.This review aims to discuss the potential of white matter as a therapeutic target for neuroprotection in lesions and diseases of the central nervous system.Pivot conditions are discussed,specifically multiple scle rosis as a white matter disease;spinal cord injury,the acute lesion of a central nervous system component where white matter prevails over the gray matte r,and Alzheimer's disease,where the white matter was considered an ancilla ry component until recently.We first describe oligodendrocyte precursor cell biology and developmental myelination,and its regulation by thyroid hormones,then briefly describe white matter imaging techniques,which are providing information on white matter involvement in central nervous system lesions and degenerative diseases.Finally,we discuss pathological mechanisms which interfere with myelin repair in adulthood.

Over-feeding the gut microbiome: A scoping review on health implications and therapeutic perspectives

The human gut microbiome has gained increasing attention over the past two decades.Several findings have shown that this complex and dynamic microbial ecosystem can contribute to the maintenance of host health or,when subject to imbalances,to the pathogenesis of various enteric and non-enteric diseases.This scoping review summarizes the current knowledge on how the gut microbiota and microbially-derived compounds affect host metabolism,especially in the context of obesity and related disorders.Examples of microbiome-based targeted intervention strategies that aim to restore and maintain an eubiotic layout are then discussed.Adjuvant therapeutic interventions to alleviate obesity and associated comorbidities are traditionally based on diet modulation and the supplementation of prebiotics,probiotics and synbiotics.However,these approaches have shown only moderate ability to induce sustained changes in the gut microbial ecosystem,making the development of innovative and tailored microbiome-based intervention strategies of utmost importance in clinical practice.In this regard,the administration of next-generation probiotics and engineered microbiomes has shown promising results,together with more radical intervention strategies based on the replacement of the dysbiotic ecosystem by means of fecal microbiota transplantation from healthy donors or with the introduction of synthetic communities specifically designed to achieve the desired therapeutic outcome.Finally,we provide a perspective for future translational investigations through the implementation of bioinformatics approaches,including machine and deep learning,to predict health risks and therapeutic outcomes.

Oligodendrocytes in a dish for the drug discovery pipeline:the risk of oversimplification

Myelination,remyelination and demyelination:modeling the in vitro drug discovery pipeline:Demyelination is a multifactorial event occurring in diseases primarily involving myelin forming cells(oligodendrocytes,OLs)and their precursors(oligodendrocyte precursor cells,OPCs)such as multiple sclerosis,but is also involved in the pathology of other central nervous system(CNS)injuries and diseases,such as neonatal encephalopathy。

Enzyme-Containing Paints Inhibit the Growth of Marine Microorganisms

A new strategy to prevent the biofouling of water-submerged surfaces is presented here. In particular, the authors showthat carbonic anydrase from Methanosarcina thermophila can be entrapped into polyacrylic paints, preserving enzyme activity. In addition, the authors also show that enzyme-containing paints inhibit the growth of marine microorganims, preventing biofouling.

Biological Activity of <i>Spartium junceum</i>L. (Fabaceae) Aromatic Water

In this study, antimicrobial, antioxidant and cytotoxic activities of Spartium junceum L. aromatic water (SJAW), obtained by vacuum process distillation, were investigated. Antimicrobial activity of SJAW was evaluated against fungal organisms, Gram-positive and Gram-negative bacteria using agar-well diffusion method. Moreover, the ability of SJAW to sensitize Staphyloccus aureus to antibiotics was also evaluated. The antioxidant activity was examined by 2,2’-diphenyl-1-picrylhydrazyl (DPPH) radical scavenging activity assay and the cytotoxic activity of SJAW main components was tested on melanoma RPMI 7932 and normal keratinocytes NCTC 2544 cell lines using the trypan blue method. The preparation did not show antibacterial activity against tested microorganisms and was unable, at tested concentrations/conditions, to sensitize Staphylococcus aureus to antibiotics clindamycin (2 μg) and tetracycline (30 μg). On the contrary SJAW possesses an appreciable antioxidant and cytotoxic activity suggesting its potential use for pharmaceutical applications.

3D imaging lipidometry in single cell by in-flow holographic tomography

The most recent discoveries in the biochemical field are highlighting the increasingly important role of lipid droplets(LDs)in several regulatory mechanisms in living cells.LDs are dynamic organelles and therefore their complete characterization in terms of number,size,spatial positioning and relative distribution in the cell volume can shed light on the roles played by LDs.Until now,fluorescence microscopy and transmission electron microscopy are assessed as the gold standard methods for identifying LDs due to their high sensitivity and specificity.However,such methods generally only provide 2D assays and partial measurements.Furthermore,both can be destructive and with low productivity,thus limiting analysis of large cell numbers in a sample.Here we demonstrate for the first time the capability of 3D visualization and the full LD characterization in high-throughput with a tomographic phase-contrast flow-cytometer,by using ovarian cancer cells and monocyte cell lines as models.A strategy for retrieving significant parameters on spatial correlations and LD 3D positioning inside each cell volume is reported.The information gathered by this new method could allow more in depth understanding and lead to new discoveries on how LDs are correlated to cellular functions.

Post-COVID-19 cholangiopathy:A systematic review

BACKGROUND The recent and still ongoing pandemic caused by the severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)entailed various long-term complications,including post-infectious cholangiopathy.AIM To identify the available studies concerning post-coronavirus disease 2019(COVID-19)cholangiopathy.METHODS An extensive bibliographical search was carried out in PubMed and in Cochrane Library to identify the articles(retrospective and prospective studies,cohort studies,case series and case reports)published between January 1,2020 and August 22,2022,using both MeSH terms and free-language keywords:cholangiopathy;COVID-19;post-COVID-19 cholangiopathy;SARS-CoV-2.RESULTS Thirteen studies fulfilled the inclusion criteria,which included 64 patients suffering from this condition.The patients were male in 82.8%of cases.Liver transplant was executed in 6 patients and scheduled in 7 patients,while 2 patients refused the surgical approach.Therefore in 23.4%of the cases,performing this procedure appeared to be necessary.CONCLUSION This review has revealed that generally the involvement of the liver in the course of SARS-CoV-2 infection is mild and transient,inducing cholestasis of cholangiocytes but can also be severe enough to cause organ failure in some cases.

High-Resolution Crystal Structure and Redox Properties of Chloroplastic Triosephosphate Isomerase from Chlamydomonas reinhardtii

Triosephosphate isomerase （TPI） catalyzes the interconversion of glyceraldehyde-3-phosphate to dihydroxyacetone phosphate. Photosynthetic organisms generally contain two isoforms of TPI located in both cytoplasm and chloroplasts. While the cytoplasmic TPI is involved in the glycolysis, the chloroplastic isoform participates in the Calvin-Benson cycle, a key photosynthetic process responsible for carbon fixation. Compared with its cytoplasmic counterpart, the functional features of chloroplastic TPI have been poorly investigated and its three-dimensional structure has not been solved. Recently, several studies proposed TPI as a potential target of different redox modifications including dithiol/disulfide interchanges, glutathionylation, and nitrosylation. However, neither the effects on protein activity nor the molecular mechanisms underlying these redox modifications have been investigated. Here, we have produced recombinantly and purified TPI from the unicellular green alga Chlamydomonas reinhardtii （Cr）. The biochemical properties of the enzyme were delineated and its crystallographic structure was determined at a resolution of 1.1 A. CrTPI is a homodimer with subunits containing the typical （β/α）8-barrel fold. Although no evidence for TRX regulation was obtained, CrTPI was found to undergo glutathionylation by oxidized glutathione and trans-nitrosylation by nitrosoglutathione, confirming its sensitivity to multiple redox modifications.

Ionized jet deposition of antimicrobial and stem cell friendly silver-substituted tricalcium phosphate nanocoatings on titanium alloy

Orthopedic infections pose severe societal and economic burden and interfere with the capability of the implanted devices to integrate in the host bone,thus significantly increasing implants failure rate.To address infection and promote integration,here nanostructured antibacterial and bioactive thin films are proposed,obtained,for the first time,by Ionized Jet Deposition(IJD)of silver-substituted tricalcium phosphate(Ag-TCP)targets on titanium.Coatings morphology,composition and mechanical properties are characterized and proof-of-concept of biocompatibility is shown.Antimicrobial efficacy is investigated against four Gram positive and Gram negative bacterial strains and against C.albicans fungus,by investigating the modifications in planktonic bacterial growth in the absence and presence of silver.Then,for all bacterial strains,the capability of the film to inhibit bacterial adhesion is also tested.Results indicate that IJD permits a fine control over films composition and morphology and deposition of films with suitable mechanical properties.Biological studies show a good efficacy against Escherichia coli,Staphylococcus aureus,Pseudomonas aeruginosa,Enterococcus faecalis and against fungus Candida albicans,with evidences of efficacy against planktonic growth and significant reduction of bacterial cell adhesion.No cytotoxic effects are evidenced for equine adipose tissue derived mesenchymal stem cells(ADMSCs),as no reductions are caused to cells viability and no interference is assessed in cells differentiation towards osteogenic lineage,in the presence of silver.Instead,thanks to nanostructuration and biomimetic composition,tricalcium phosphate(TCP)coatings favor cells viability,also when silver-substituted.These findings show that silver-substituted nanostructured coatings are promising for orthopedic implant applications.

Molecular alterations in pancreatic tumors

Genetic alterations in pancreatic tumors can usually be classified in:(1)Mutational activation of oncogenes;(2)Inactivation of tumor suppressor genes;and(3)Inactivation of genome maintenance genes controlling the repair of DNA damage.Endoscopic ultrasound-guided fine-needle aspiration has improved preoperative diagnosis,but the management of patients with a pancreatic lesion is still challenging.Molecular testing could help mainly in solving these“inconclusive”specimens.The introduction of multi-gene analysis approaches,such as next-generation sequencing,has provided a lot of useful information on the molecular characterization of pancreatic tumors.Different types of pancreatic tumors(e.g.,pancreatic ductal adenocarcinomas,intraductal papillary mucinous neoplasms,solid pseudopapillary tumors)are characterized by specific molecular alterations.The aim of this review is to summarize the main molecular alterations found in pancreatic tumors.

TRPA1 Is Expressed in Central But Not in Peripheral Glia

TRPA1 are cation channels expressed in sensory neurons and in several other cell types. This channel is specifically activated by ally isothiocyanate (AITC), the pungent component of mustard oil, as well as by other electrophilic compounds. Although TRPA1 expression in central glia has been reported, its subcellular localization and its expression in peripheral glia have not been investigated before. In this paper we report the molecular and functional expression of TRPA1 in rat cortical astrocytes. Real-time RT-PCR identified low but significant amounts of TRPA1 mRNA in cortical astrocytes while no signal was seen in peripheral glia isolated from dorsal root ganglia (DRG) or in a glial cell line (DITNC-1). Calcium imaging showed AITC-induced signals in astro-cytes while no response in peripheral glia. AITC induced calcium signals in astrocytes in the presence and in the absence of extracellular calcium, suggesting an intracellular localization of TRPA1 channels. Whole cell electrophysiological recordings were performed in astrocytes, in peripheral glia and in DITNC-1 cells transfected with TRPA1 during AITC application. In TRPA1-transfected DITNC-1 cells typical TRPA1 currents were recorded with a reversal potential near 0 mV, consistent with the opening of a non-selective cation channel. No such currents were recorded in untransfected DITNC-1 cells, in astrocytes and in peripheral glial cells, where even high concentrations of AITC (up to 10 mM) induced no significant outward current. In astrocytes AITC transiently induced an outward rectifying current with the reversal potential near ?90 mV, consistent with K channel activation, likely activated by intracellular release of calcium. Our results suggest that TRPA1 channels are molecularly and functionally expressed in calcium-containing organelles of rat cortical astrocytes, with no expression in the plasma membrane.

Somatic pharmacogenomics of gastrointestinal stromal tumor

Gastrointestinal stromal tumors(GISTs)are rare entities,which,however,represent the most common mesenchymal tumor of the gastrointestinal tract.The discovery of gain of function mutations on KIT and PDGFRA receptor genes led to a deep revolution in the knowledge of this tumor.This paved the way to the introduction of imatinib and other tyrosine-kinase inhibitors(TKIs),which terrifically revolutionized the prognosis of GIST patients.Currently,it is well established that tumor mutational status is the main player in clinical outcome;however,with the research advances,it has been slowly understood that GIST landscape is more complex than expected and the TKIs available are not effective for all the GIST subtypes.For this reason,in the era of tailored/personalized medicine,each GIST patient should be considered individually and genetic consult should be the first step to take in consideration in the therapeutic decision making process.