Zinc pretreatment for protection against intestinal ischemiareperfusion injury

BACKGROUND Intestinal ischemia-reperfusion(I/R)injury(II/RI)is a critical condition that results in oxidative stress,inflammation,and damage to multiple organs.Zinc,an essential trace element,offers protective benefits in several tissues during I/R injury,but its effects on intestinal II/RI remain unclear.METHODS C57BL/6 mice were pretreated with zinc sulfate(ZnSO4,10 mg/kg)daily for three days before I/R injury was induced via superior mesenteric artery occlusion(SMAO)and abdominal aortic occlusion(AAO)models.Tissue and serum samples were collected to evaluate intestinal,liver,and kidney damage using Chiu’s score,Suzuki score,and histopathological analysis.Caco-2 cells and intestinal organoids were used for in vitro hypoxia-reoxygenation injury models to measure reactive oxygen species(ROS)and superoxide dismutase(SOD)levels.RESULTS Zinc pretreatment significantly reduced intestinal damage in the SMAO and AAO models(P<0.001).The serum levels of liver enzymes(alanine aminotransferase,aspartate aminotransferase)and kidney markers(creatinine and urea)were lower in the zinc-treated mice than in the control mice,indicating reduced hepatic and renal injury.In vitro,zinc decreased ROS levels and increased SOD activity in Caco-2 cells subject to hypoxia-reoxygenation injury.Intestinal organoids pretreated with zinc exhibited enhanced resilience to hypoxic injury compared to controls.CONCLUSION Zinc pretreatment mitigates II/RI and reduces associated multiorgan damage.These findings suggest that zinc has potential clinical applications in protecting against I/R injuries.

Late effects of the treatment of childhood cancer

Excellent progress has been made in the last few decades in the cure rates of pediatric malignancies,with more than 80%of children with cancer who have access to contemporary treatment being cured.However,the therapies responsible for this survival can also produce adverse physical and psychological long-term outcomes,referred to as late effects,which appear months to years after the completion of cancer treatment.Research has shown that 60%to 90%of childhood cancer survivors(CCSs)develop one or more chronic health conditions,and 20%to 80%of survivors experience severe or life-threatening complications during adulthood.Therefore,understanding the late side effects of such treatments is important to improve the health and quality of life of the growing population of CCSs.

Pathogenesis, diagnosis, and treatment of epilepsy: electromagnetic stimulation-mediated neuromodulation therapy and new technologies

Epilepsy is a severe,relapsing,and multifactorial neurological disorder.Studies regarding the accurate diagnosis,prognosis,and in-depth pathogenesis are crucial for the precise and effective treatment of epilepsy.The pathogenesis of epilepsy is complex and involves alterations in variables such as gene expression,protein expression,ion channel activity,energy metabolites,and gut microbiota composition.Satisfactory results are lacking for conventional treatments for epilepsy.Surgical resection of lesions,drug therapy,and non-drug interventions are mainly used in clinical practice to treat pain associated with epilepsy.Non-pharmacological treatments,such as a ketogenic diet,gene therapy for nerve regeneration,and neural regulation,are currently areas of research focus.This review provides a comprehensive overview of the pathogenesis,diagnostic methods,and treatments of epilepsy.It also elaborates on the theoretical basis,treatment modes,and effects of invasive nerve stimulation in neurotherapy,including percutaneous vagus nerve stimulation,deep brain electrical stimulation,repetitive nerve electrical stimulation,in addition to non-invasive transcranial magnetic stimulation and transcranial direct current stimulation.Numerous studies have shown that electromagnetic stimulation-mediated neuromodulation therapy can markedly improve neurological function and reduce the frequency of epileptic seizures.Additionally,many new technologies for the diagnosis and treatment of epilepsy are being explored.However,current research is mainly focused on analyzing patients’clinical manifestations and exploring relevant diagnostic and treatment methods to study the pathogenesis at a molecular level,which has led to a lack of consensus regarding the mechanisms related to the disease.

Controversies around the treatment of peritoneal metastases of colorectal cancer

In this editorial we examine the article by Wu et al published in the World Journal of Gastrointestinal Oncology.Surgical resection for peritoneal metastases from colorectal cancer(CRC)has been gradually accepted in the medical oncology community.A randomized trial(PRODIGE 7)on cytoreductive surgery(CRS)with hyperthermic intraperitoneal chemotherapy(HIPEC)failed to prove any benefit of oxaliplatin in the overall survival of patients with peritoneal metastases from colorectal origin.Nevertheless,isolated systemic chemotherapy for CRC stage IV has demonstrated a reduced response in peritoneal metastases than that obtained in other metastatic sites such as the liver.Another tool is required in those patients to achieve more local control of the disease.Surgical groups in peritoneal surgery continue to use HIPEC in their procedures,using other agents than oxaliplatin for peritoneal cavity infusion,such as mitomycin C.These patients present with complex surgical issues to manage,and consequently a large burden of complications has to be anticipated.Therefore,identifying patients who will benefit from CRS with or without HIPEC would be of great interest.

Advancing treatment strategies:Insights from network meta-analysis of hepatic arterial infusion chemotherapy for advanced hepatocellular carcinoma

This study examines the pivotal findings of the network meta-analysis of Zhou et al,which evaluated the efficacy of hepatic arterial infusion chemotherapy and combination therapies for advanced hepatocellular carcinoma(HCC).This meta-analysis suggests that therapeutic combinations have greater efficacy than do standard treatments.The article highlights the key insights that have the potential to shift current clinical practice and enhance outcomes for patients with advanced HCC.Additionally,this article discusses further research that can be conducted to optimize these treatments and achieve personalized care for patients with HCC.

Efficacy,safety and treatment satisfaction of transition to a regimen of insulin degludec/aspart:A pilot study

BACKGROUND There is a lack of clinical evidence on the efficacy and safety of transitioning from a thrice-daily pre-mixed insulin or basal-prandial regimen to insulin degludec/aspart(IDegAsp)therapy,with insufficient data from the Chinese population.AIM To demonstrate the efficacy,safety,and treatment satisfaction associated with the transition to IDegAsp in type 2 diabetes mellitus(T2DM).METHODS In this 12-week open-label,non-randomized,single-center,pilot study,patients with T2DM receiving thrice-daily insulin or intensive insulin treatment were transitioned to twice-daily injections of insulin IDegAsp.Insulin doses,hemoglobin A1c(HbA1c)levels,fasting blood glucose(FBG),hypoglycemic events,a Diabetes Treatment Satisfaction Questionnaire,and other parameters were assessed at baseline and 12-weeks.RESULTS This study included 21 participants.A marked enhancement was observed in the FBG level(P=0.02),daily total insulin dose(P=0.03),and overall diabetes treatment satisfaction(P<0.01)in the participants who switched to IDegAsp.There was a decrease in HbA1c levels(7.6±1.1 vs 7.4±0.9,P=0.31)and the frequency of hypoglycemic events of those who switched to IDegAsp decreased,however,there was no statistically significant difference.CONCLUSION The present findings suggest that treatment with IDegAsp enhances clinical outcomes,particularly FBG levels,daily cumulative insulin dose,and overall satisfaction with diabetes treatment.

The emerging role of mesenchymal stem cell-derived extracellular vesicles to ameliorate hippocampal NLRP3 inflammation induced by binge-like ethanol treatment in adolescence

Our previous studies have reported that activation of the NLRP3(NOD-,LRR-and pyrin domain-containing protein 3)-inflammasome complex in ethanol-treated astrocytes and chronic alcohol-fed mice could be associated with neuroinflammation and brain damage.Mesenchymal stem cell-derived extracellular vesicles(MSC-EVs)have been shown to restore the neuroinflammatory response,along with myelin and synaptic structural alterations in the prefrontal cortex,and alleviate cognitive and memory dysfunctions induced by binge-like ethanol treatment in adolescent mice.Considering the therapeutic role of the molecules contained in mesenchymal stem cell-derived extracellular vesicles,the present study analyzed whether the administration of mesenchymal stem cell-derived extracellular vesicles isolated from adipose tissue,which inhibited the activation of the NLRP3 inflammasome,was capable of reducing hippocampal neuroinflammation in adolescent mice treated with binge drinking.We demonstrated that the administration of mesenchymal stem cell-derived extracellular vesicles ameliorated the activation of the hippocampal NLRP3 inflammasome complex and other NLRs inflammasomes(e.g.,pyrin domain-containing 1,caspase recruitment domain-containing 4,and absent in melanoma 2,as well as the alterations in inflammatory genes(interleukin-1β,interleukin-18,inducible nitric oxide synthase,nuclear factor-kappa B,monocyte chemoattractant protein-1,and C–X3–C motif chemokine ligand 1)and miRNAs(miR-21a-5p,miR-146a-5p,and miR-141-5p)induced by binge-like ethanol treatment in adolescent mice.Bioinformatic analysis further revealed the involvement of miR-21a-5p and miR-146a-5p with inflammatory target genes and NOD-like receptor signaling pathways.Taken together,these findings provide novel evidence of the therapeutic potential of MSC-derived EVs to ameliorate the hippocampal neuroinflammatory response associated with NLRP3 inflammasome activation induced by binge drinking in adolescence.

Variations in quantifying patient reported outcome measures to estimate treatment effect

In the practice of healthcare,patient-reported outcomes(PROs)and PRO measures(PROMs)are used as an attempt to observe the changes in complex clinical situations.They guide us in making decisions based on the evidence regarding patient care by recording the change in outcomes for a particular treatment to a given condition and finally to understand whether a patient will benefit from a particular treatment and to quantify the treatment effect.For any PROM to be usable in health care,we need it to be reliable,encapsulating the points of interest with the potential to detect any real change.Using structured outcome measures routinely in clinical practice helps the physician to understand the functional limitation of a patient that would otherwise not be clear in an office interview,and this allows the physician and patient to have a meaningful conver-sation as well as a customized plan for each patient.Having mentioned the rationale and the benefits of PROMs,understanding the quantification process is crucial before embarking on management decisions.A better interpretation of change needs to identify the treatment effect based on clinical relevance for a given condition.There are a multiple set of measurement indices to serve this effect and most of them are used interchangeably without clear demarcation on their differences.This article details the various quantification metrics used to evaluate the treatment effect using PROMs,their limitations and the scope of usage and implementation in clinical practice.

Selective reduction process of zinc ferrite and its application in treatment of zinc leaching residues

The traditional zinc hydro-metallurgy generates a large amount of zinc ferrite residue rich in valuable metals. The separation of iron is crucial for resource recycling of valuable metals in zinc ferrite residue. A novel selective reduction roasting？leaching process was proposed to separate zinc and iron from zinc leaching residue which contains zinc ferrite. The thermodynamic analysis was employed to determine the predominant range of Fe3O4 and ZnO during reduction roasting process of zinc ferrite. Based on the result of thermodynamic calculation, we found thatV（CO）/V（CO＋CO2） ratio is a key factor determining the phase composition in the reduction roasting product of zinc ferrite. In the range ofV（CO）/V（CO＋CO2） ratio between 2.68% and 36.18%, zinc ferrite is preferentially decomposed into Fe3O4 and ZnO. Based on thermogravimetric （TG） analysis, the optimal conditions for reduction roasting of zinc ferrite are determined as follows： temperature 700？750 °C, volume fraction of CO 6% and V（CO）/V（CO＋CO2） ratio 30%. Based on the above results, zinc leaching residue rich in zinc ferrite was roasted and the roasted product was leached by acid solution. It is found that zinc extraction rate in zinc leaching residue reaches up to 70% and iron extraction rate is only 18.4%. The result indicates that zinc and iron can be effectively separated from zinc leaching residue.

Life cycle assessment for waste acid treatment in zinc smelting

Lift cycle assessment(LCA)methodology was applied to evaluating and comparing two waste acid disposal processes in zinc smelting.The results indicate that environmental impacts of gas−liquid vulcanization technologies are human toxicity,abiotic depletion potential,and global warming risk,which are mainly caused in neutralizing−evaporating−crystallization unit and electrodialysis unit.As for traditional lime neutralization method,vulcanization unit is the main factor.In this regard,the total environmental impact of traditional lime neutralization method is much higher than that of gas−liquid vulcanization technologies.Furthermore,the sensitive analysis shows that electricity and sodium sulfide(60%)are sensitive factors in two waste acid disposal technologies.In addition,the total cost of disposing a functional unit waste acid in traditional lime neutralization process is nearly 27 times that of the gas−liquid vulcanization waste acid disposal technologies.

Biological treatment of wastewater with high concentrations of zinc and sulfate ions from zinc pyrithione synthesis

An enriched and domesticated bacteria consortium of sulfate-reducing bacteria(SRB)was used to treat wastewater from zinc pyrithione(ZPT)production,and the effects of different reaction parameters on sulfate reduction and zinc precipitation were evaluated.The single-factor experimental results showed that the removal rates of Zn2+and24SO?decreased with an increased ZPT concentration ranging from3.0to5.0mg/L.Zn2+and24SO?in wastewater were effectively removed under the conditions of30?35°C,pH7?8and an inoculum concentration of10%?25%.The presence of Fe0in the SRB system enhanced Zn2+and24SO?removal and may increase the resistance of SRB to the toxicity of Zn2+and ZPT in wastewater.A Box?Behnken design was used to evaluate the influence of the main operating parameters on the removal rate of24SO?.The optimum parameter values were found to be pH7.45,33.61°C and ZPT concentration of0.62mg/L,and the removal rate of24SO?reached a maximum of91.62%under these optimum conditions.

Effects of microwave pretreatment on zinc extraction from spent catalyst saturated with zinc acetate

A new technology for microwave pretreatment of spent catalyst on Zn extraction by HCl leaching was proposed and the temperature-change curve of spent catalyst under microwave irradiation was measured.The influence of microwave pretreatment temperature and microwave irradiation time on zinc extraction was investigated and the mechanism of microwave pretreatment for spent catalyst was analyzed.The results show that microwave pretreatment can greatly enhance the leaching rate of Zn.The Zn extraction reaches 96.58%under the conditions of microwave pretreatment temperature of 950℃and the microwave irradiation time of 12 min.The blocked pores of spent catalyst can be opened through microwave pretreatment,increasing the contact area of leaching reagent and zinc.

Treatment of zinc deficiency without zinc fortification

Zinc(Zn) deficiency in animals became of interest until the 1950s.In this paper,progresses in researches on physiology of Zn deficiency in animals,phytate effect on bioavailability of Zn,and role of phytase in healing Zn deficiency of animals were reviewed.Several studies demonstrated that Zn is recycled via the pancreas;the problem of Zn deficiency was controlled by Zn homeostasis.The endogenous secretion of Zn is considered as an important factor influencing Zn deficiency,and the critical molar ratio is 10.Phytate(inositol hexaphosphate) constituted up to 90% of the organically bound phosphorus in seeds.Great improvement has been made in recent years on isolating and measuring phytate,and its structure is clear.Phytate is considered to reduce Zn bioavailability in animal.Phytase is the enzyme that hydrolyzes phytate and is present in yeast,rye bran,wheat bran,barley,triticale,and many bacteria and fungi.Zinc nutrition and bioavailability can be enhanced by addition of phytase to animal feeds.Therefore,using phytase as supplements,the most prevalent Zn deficiency in animals may be effectively corrected without the mining and smelting of several tons of zinc daily needed to correct this deficiency by fortification worldwide.

Study on the pre-treatment of oxidized zinc ore prior to flotation

The pre-treatment of zinc oxide bearing ores with high slime content is important to ensure that resources are utilized optimally. This paper reports an improved process using hydrocyclone de-sliming, dispersion reagents, and magnetic removal of iron minerals for the pre-treatment of zinc oxide ore with a high slime and iron content, and the benefits compared to traditional technologies are shown. In addition, this paper investigates the damage related to fine slime and iron during zinc oxide flotation, the necessity of using hydrocyclone de-sliming together with dispersion reagents to alleviate the influence of slime, and interactions among hydrocyclone de-sliming, reagent dispersion, and magnetic iron removal. Results show that under optimized operating conditions the entire beneficiation technology results in a flotation concentrate with a Zn grade of 34.66% and a recovery of 73.41%.

Acceptability and Compliance to a 10-Day Regimen of Zinc Treatment in Diarrhea in Rural Bangladesh

We hypothesised that the promotion of blister packs of zinc may be carried out by health personnel in health care facilities to the mothers of children suffering from diarrhea. We predicted that good acceptability and good compliance to zinc treatment in rural Bangladesh would be over 75% and at least 60%, respectively. Between January and December 2011, six hundred and thirty five children aged 6 - 59 months who presented with acute diarrhea received a 10-day zinc regimen. Determination of acceptability and compliance of a dispersible zinc tablet in children 6 - 59 months old was main point of the study. In-home follow-ups started within 2 - 3 weeks after the regimen began. Seventy seven percent of the mothers/caretakers perceived that the taste of the zinc tablets was the same or better than that of other medicines given to their children and expressed willingness to use zinc in the future (good acceptability). Sixty-two percent of the children completed full 10-day course of zinc treatment by taking one tablet a day that had been completely dissolved in a small amount of water (good compliance). There was 63% excess risk for poor compliance to zinc if father stays at home with the family [OR = 1.63 (95%CI;1.09, 2.46) p = 0.019]. Despite vomiting, 33% children continued to receive zinc tablet [OR = 0.67 (95%CI;(0.47, 0.97, 0.032)] after adjusting for co-variates. Both acceptability and compliance to dispersible zinc tablets in childhood diarrheal illnesses are still not at the expected level in rural Bangladesh.

Effect of zinc treatment on clinical outcomes in patients with liver cirrhosis:A systematic review and meta-analysis

BACKGROUNDZinc is an essential trace element integral to many cellular and immune functions.Zinc deficiency is highly prevalent in patients with cirrhosis and related to diseaseseverity.AIMTo evaluate whether zinc supplementation improves clinical outcomes (diseaseseverity and mortality) in patients with cirrhosis.METHODSThis prospectively registered systematic review (PROSPERO reference:CRD42018118219) included all studies in Medline, Embase or Cochrane databasewith inclusion criteria of adult human studies, comparing zinc supplementationof at least 28 d with standard care or placebo in patients with cirrhosis. Mortalityand clinical severity score data were extracted. Random effects meta-analysescompared mortality at 6 mo and 2 years. Risk of bias was assessed using theNational Institutes of Health quality assessment tool.RESULTSSeven hundred and twelve articles were identified of which four were eligible.Zinc formulations and doses varied (elemental zinc 3.4-214 mg daily) for different intervention periods in patients with differing etiology and severity of cirrhosis.Two studies were considered to be at high risk of bias. There was no significantdifference in 6-mo mortality between patients treated with zinc versus controls[risk ratio 0.98 (0.90-1.05)]. Changes in severity scores were not reported in anystudy.CONCLUSIONZinc supplementation is not associated with reduced mortality in patients withcirrhosis. Findings are limited by the small number of eligible studies andsignificant heterogeneity in intervention and patient population.

Therapeutic Evaluation of 2% Tea Lotion in Comparison with 5% Zinc Sulfate Solution in the Treatment of Acne Rosacea

Background: There are many effective topical and systemic therapies for acne rosacea. Topical zinc sulfate and tea lotion have been used in treatment of acne vulgaris. Objectives: To evaluate effectiveness of 2% tea lotion in comparison with 5% zinc sulfate solution in the treatment of acne rosacea. Patients and Methods: This single, blinded, comparative therapeutic clinical trial was carried out in the Department of Dermatology—Baghdad Teaching Hospital from June 2006-December 2007. Twenty two patients with acne rosacea were divided into two groups and were instructed to apply the following lotions for two months, Group A used 2% tea lotion twice daily while Group B used 5% zinc sulfate solution twice daily. Patient with severe acne rosacea were excluded from the study. Clinical improvement was evaluated every 2 weeks by determination of the disease severity score (Sharquie’s score) before and after treatment. Results: Eighteen patients with acne rosacea completed the study with their ages ranging from 26 - 70 (40.5 ± 10.9) years. For Group A and Group B were 39.7 ± 8.2, 41.2 ± 13.1 years respectively, with eight patients in Group A, ten patients in Group B. Five percent zinc sulfate solution was statistically significant in reducing the disease severity score in acne rosacea, while 2% tea lotion was beneficial but did not reach statistically significant level as zinc sulfate solution. Conclusion: Five percent zinc sulfate solution was a good alternative remedy to be used in patients with acnerosacea.

Treatment of Acute Cutaneous Leishmaniasis by Oral Zinc Sulfate and Oral Ketocanazole Singly and in Combination

Background: Cutaneous Leishmaniasis (CL) is an endemic disease in many countries and caused by different species of Leishmania parasite. It results in a deformed scar after a relatively long period. Many therapies have been tried in treatment of this disease. Objective: To compare the effect of oral zinc sulfate and oral ketoconazole singly and in combination in the treatment of acute cutaneous leishmaniasis. Patients and Methods: This single, blinded, therapeutic, controlled study was conducted in the Department of Dermatology, Baghdad Teaching Hospital, Baghdad, Iraq, during the period, January 2015 to July 2015. Seventy-five patients with acute CL were enrolled in this study. The total numbers of lesions were 327, and the duration of lesions ranged from 4 to 12 (6.9 ± 0.7) weeks. The diagnosis was confirmed by smear and histopathology. Patients were divided into three groups: 24 patients in Group A were treated with oral zinc sulfate capsules 10 mg/kg/day for 6 weeks;24 patients in Group B were treated with ketoconazole tablets 200 mg twice daily for 6 weeks and 27 patients in Group C were treated orally with a combination of zinc sulfate and ketoconazole for 6 weeks. All patients were seen regularly every 2 weeks for 6 weeks of treatment period, then monthly for the next three months as follow up period. Healing of the lesions was assessed by using Sharquie’s modified Leishmania score to assess the objective response to the topical or systemic therapy. Results:After six weeks, 75 patients have completed the treatment, 24patients received zinc sulfate capsule, 24 patients received oral ketoconazole and 27 patients received a combination of both treatments. The cure rate was (60%) in the group receiving oral zinc sulfate capsuleand (50%) in the one receiving oral ketoconazole tablet (P = 0.146) and (96%) in the combination group (P ? 0.04). Conclusion: The combination therapy using oral zinc sulfate and oral ketoconazole gave a high cure rate. The combination therapy is a new mode of therapy as both drugs act in a synergistic way.

Design Strategies for Aqueous Zinc Metal Batteries with High Zinc Utilization: From Metal Anodes to Anode-Free Structures

Aqueous zinc metal batteries(AZMBs)are promising candidates for next-generation energy storage due to the excellent safety, environmental friendliness, natural abundance, high theoretical specific capacity, and low redox potential of zinc(Zn) metal. However,several issues such as dendrite formation, hydrogen evolution, corrosion, and passivation of Zn metal anodes cause irreversible loss of the active materials. To solve these issues, researchers often use large amounts of excess Zn to ensure a continuous supply of active materials for Zn anodes. This leads to the ultralow utilization of Zn anodes and squanders the high energy density of AZMBs. Herein, the design strategies for AZMBs with high Zn utilization are discussed in depth, from utilizing thinner Zn foils to constructing anode-free structures with theoretical Zn utilization of 100%, which provides comprehensive guidelines for further research. Representative methods for calculating the depth of discharge of Zn anodes with different structures are first summarized. The reasonable modification strategies of Zn foil anodes, current collectors with pre-deposited Zn, and anode-free aqueous Zn metal batteries(AF-AZMBs) to improve Zn utilization are then detailed. In particular, the working mechanism of AF-AZMBs is systematically introduced. Finally, the challenges and perspectives for constructing high-utilization Zn anodes are presented.

An Electrochemical Perspective of Aqueous Zinc Metal Anode

Based on the attributes of nonflammability,environmental benignity,and cost-effectiveness of aqueous electrolytes,as well as the favorable compatibility of zinc metal with them,aqueous zinc ions batteries(AZIBs)become the leading energy storage candidate to meet the requirements of safety and low cost.Yet,aqueous electrolytes,acting as a double-edged sword,also play a negative role by directly or indirectly causing various parasitic reactions at the zinc anode side.These reactions include hydrogen evolution reaction,passivation,and dendrites,resulting in poor Coulombic efficiency and short lifespan of AZIBs.A comprehensive review of aqueous electrolytes chemistry,zinc chemistry,mechanism and chemistry of parasitic reactions,and their relationship is lacking.Moreover,the understanding of strategies for suppressing parasitic reactions from an electrochemical perspective is not profound enough.In this review,firstly,the chemistry of electrolytes,zinc anodes,and parasitic reactions and their relationship in AZIBs are deeply disclosed.Subsequently,the strategies for suppressing parasitic reactions from the perspective of enhancing the inherent thermodynamic stability of electrolytes and anodes,and lowering the dynamics of parasitic reactions at Zn/electrolyte interfaces are reviewed.Lastly,the perspectives on the future development direction of aqueous electrolytes,zinc anodes,and Zn/electrolyte interfaces are presented.