Comprehensive Application of Graphene: Emphasis on Biomedical Concerns

Graphene, sp^2 hybridized carbon framework of one atom thickness, is reputed as the strongest material to date. It has marked its impact in manifold applications including electronics, sensors, composites, and catalysis. Current state-of-the-art graphene research revolves around its biomedical applications. The two-dimensional(2D) planar structure of graphene provides a large surface area for loading drugs/biomolecules and the possibility of conjugating fluorescent dyes for bioimaging. The high near-infrared absorbance makes graphene ideal for photothermal therapy. Henceforth, graphene turns out to be a reliable multifunctional material for use in diagnosis and treatment. It exhibits antibacterial property by directly interacting with the cell membrane. Potential application of graphene as a sca old for the attachment and proliferation of stem cells and neuronal cells is captivating in a tissue regeneration scenario. Fabrication of 2D graphene into a 3D structure is made possible with the help of 3D printing, a revolutionary technology having promising applications in tissue and organ engineering. However, apart from its advantageous application scope, use of graphene raises toxicity concerns. Several reports have confirmed the potential toxicity of graphene and its derivatives, and the inconsistency may be due to the lack of standardized consensus protocols. The present review focuses on the hidden facts of graphene and its biomedical application, with special emphasis on drug delivery, biosensing, bioimaging, antibacterial, tissue engineering, and 3D printing applications.

Mitochondria: A critical hub for hepatic stellate cells activation during chronic liver diseases

Background: Upon liver injury, quiescent hepatic stellate cells(q HSCs), reside in the perisinusoidal space, phenotypically transdifferentiate into myofibroblast-like cells(MFBs). The q HSCs in the normal liver are less fibrogenic, migratory, and also have less proliferative potential. However, activated HSCs(a HSCs) are more fibrogenic and have a high migratory and proliferative MFBs phenotype. HSCs activation is a highly energetic process that needs abundant intracellular energy in the form of adenosine triphosphate(ATP) for the synthesis of extracellular matrix(ECM) in the injured liver to substantiate the injury. Data sources: The articles were collected through Pub Med and EMBASE using search terms "mitochondria and hepatic stellate cells", "mitochondria and HSCs", "mitochondria and hepatic fibrosis", "mitochondria and liver diseases", and "mitochondria and chronic liver disease", and relevant publications published before September 31, 2020 were included in this review. Results: Mitochondria homeostasis is affected during HSCs activation. Mitochondria in a HSCs are highly energetic and are in a high metabolically active state exhibiting increased activity such as glycolysis and respiration. a HSCs have high glycolytic enzymes expression and glycolytic activity induced by Hedgehog(Hh) signaling from injured hepatocytes. Increased glycolysis and aerobic glycolysis(Warburg effect) endproducts in a HSCs consequently activate the ECM-related gene expressions. Increased Hh signaling from injured hepatocytes downregulates peroxisome proliferator-activated receptor-γ expression and decreases lipogenesis in a HSCs. Glutaminolysis and tricarboxylic acid cycle liberate ATPs that fuel HSCs to proliferate and produce ECM during their activation. Conclusions: Available studies suggest that mitochondria functions can increase in parallel with HSCs activation. Therefore, mitochondrial modulators should be tested in an elaborate manner to control or prevent the HSCs activation during liver injury to subsequently regress hepatic fibrosis.

Azoxymethane-induced rat aberrant crypt foci:Relevance in studying chemoprevention of colon cancer

The pathogenesis of colon cancer involves sequential and multistep progression of epithelial cells initiated to a cancerous state with defined precancerous intermediaries. Aberrant crypt foci （ACF） represent the earliest identifiable intermediate precancerous lesions during colon carcinogenesis in both laboratory animals and humans. ACF are easily induced by colon-specific carcinogens in rodents and can be used to learn more about the process of colon carcinogenesis. For over two decades, since its first discovery, azoxymethane （AOM）-induced rodent ACF have served as surrogate biomarkers in the screening of various anticarcinogens and carcinogens. Several dietary constituents and phytochemicals have been tested for their colon cancer chemopreventive efficacy using the ACF system. There has been substantial effort in defining and refining ACF in terms of understanding their molecular make-up, and extensive research in this field is currently in progress. In chemoprevention studies, AOM-induced rat ACF have been very successful as biomarkers, and have provided several standardized analyses of data. There have been several studies that have reported that ACF data do not correlate to actual colon tumor outcome, however, and hence there has been an ambiguity about their role as biomarkers. The scope of this mini-review is to provide valuable insights and limitations of AOM-induced rat ACF as biomarkers in colon cancer chemoprevention studies. The role of the dynamics and biological heterogeneity of ACF is critical in understanding them as biomarkers in chemoprevention studies.

Evaluation of spermatogenesis and fertility in F1 male rats after in utero and neonatal exposure to extremely low frequency electromagnetic fields

Aim:To determine whether in utero and neonatal exposure to a 60 Hz extremely low frequency electromagnetic field (EMF) results in spermatotoxicity and reproductive dysfunction in the F1 offspring of rats.Methods:Age-matched, pregnant Sprague-Dawley rats were exposed continuously (21 h/day) to a 60 Hz EMF at field strengths of 0 (sham control),5,83.3 or 500 μT from day 6 of gestation through to day 21 of lactation.The experimentally generated magnetic field was monitored continuously (uninterrupted monitoring over the period of the study) throughout the study.Results:No exposure-related changes were found in exposed or sham-exposed animals with respect to the anogenital distance,preputial separation,testis weight,testicular histology,sperm count,daily sperm production, sperm motility,sperm morphology and reproductive capacity of F1 offspring.Conclusion:Exposure of Sprague- Dawley rats to a 60 Hz EMF at field strengths of up to 500 μT from day 6 of gestation to day 21 of lactation did not produce any detectable alterations in offspring spermatogenesis and fertility.

Protective effects of anti-ricin A-chain RNA aptamer against ricin toxicity

AIM： To investigate the therapeutic potential of an RNA ligand （aptamer） specific for the catalytic ricin A-chain （RTA）, the protective effects of a 31-nucleo- tide RNA aptamer （31RA）, which formed a high affinity complex with RTA, against ricin-induced toxicity in cell- based luciferase translation and cell cytotoxicity assays were evaluated. METHODS： To test the therapeutic potential of anti- RTA aptamers in Chinese hamster ovary （CliO） AA8 cells stably transfected with a tetracycline regulatable promoter, ricin ribotoxicity was measured us- ing luciferase and ricin-induced cytotoxicity was ascertained by MTS cell proliferation assay with tet- razolium compound [3-（4,5-dimethylthiazol-2-yl）- 5-（3-carboxymethoxyphenyl）-2-（4-sulfophenyl）-2H- tetrazolium]. RESULTS： Inhibition of protein synthesis by ricin in CliO AA8 cells resulted in diminished luciferase activity and treatment with polyclonal antibody against degly- cosylated RTA （dgA） neutralized the inhibitory effects of ricin on luciferase activity and protected against ricin-induced cytotoxicity as measured by MTS assay. The 31RA anti-RTA aptamer inhibited the translation of luciferase mRNA in cell-free reticulocyte translation assay. 31RA aptamer also partially neutralized the inhibitory effects of ricin on luciferase activity and partially protected against ricin-induced cytotoxicity in CliO AA8 cells. CONCLUSION： We have shown that anti-RTA RNA aptamer can protect against ricin ribotoxicity in cell- based luciferase and cell cytotoxicity assays. Hence, RNA aptamer that inhibits RTA enzymatic activity represents a novel class of nucleic acid inhibitor that has the potential to be developed as a therapeutic agent for the treatment of ricin intoxication.

Serial blood concentration of polyethoxylated tallow amine and clinical presentations in acute herbicide poisoning

Most commercially available herbicides contain surfactants as co-formulants to increase adhesion and absorption by plant leaves.Ethoxylated amines,one of the most used surfactants,are non-ionic and derived from animal fats.They represent a class of surfactants with similar structural features,including polyethoxylated tallow amine(POEA).POEA is widely used in glyphosate,glufosinate-containing herbicides.In 2015,the European Food Safety Society(EFSA)concluded that POEA was more toxic than glyphosate when tested in glyphosate-based formulations.[1]They also attributed the poisoning following ingestion by humans to the presence of POEA.

Phytochemical Analysis and Antifungal Activity of Extracts from Leaves and Fruit Residues of Brazilian Savanna Plants Aiming Its Use as Safe Fungicides

The increasing demand for safe food without preservatives or pesticides residues has encouraged several studies on natural products with antifungal activity and low toxicity.In this study,ethanolic extracts from leaves and fruit residues(peel and seeds)of three Brazilian savanna species(Acrocomia aculeata,Campomanesia adamantium and Caryocar brasiliense)were evaluated against phytopathogenic fungi.Additionally,the most active extract was chemically characterized by ESI-MS and its oral acute toxicity was evaluated.Extracts from C.brasiliense(pequi)peel and leaves were active against Alternaria alternata,Alternaria solani and Venturia pirina with minimal inhibitory concentrations between 350 and 1000 lg/mL.When incorporated in solid media,these extracts extended the lag phase of A.alternata and A.solani and reduced the growth rate of A.solani.Pequi peel extract showed better antifungal activity and their ESI-MS analysis revealed the presence of substances widely reported as antifungal such as gallic acid,quinic acid,ellagic acid,glucogalin and corilagin.The oral acute toxicity was relatively low,being considered safe for use as a potential natural fungicide.

Surgical intervention for acute pancreatitis in the COVID-19 era

Approximately 15%-19%of patients with severe acute respiratory syndrome coronavirus type 2(SARS-CoV-2)infections develop gastrointestinal symptoms.Acute pancreatitis(AP)has been reported in 0.1%of patients with coronavirus disease 2019(COVID-19).Biliary AP was most common(78.4%)before the COVID-19 pandemic;idiopathic AP is most common in patients with COVID-19(up to 57.1%).The number of emergency department presentations decreased by 23.3%during the pandemic and many governments made national recommendations to delay nonurgent endoscopic procedures,leading to decrements of 22%in combined esophagogastroduodenoscopy(EGD)and colonoscopy and 20%in EGD after the COVID-19 pandemic.The symptoms and signs of COVID-19-related AP are fever(63%),abdominal pain(58%),respiratory symptoms(40%),nausea and vomiting(39%),and headache(4%).Approximately 5-10%of patients develop necrotizing or hemorrhagic AP,and patients who required surgical intervention had a higher mortality risk.Compared to 2019,the rates of elective surgery decreased by 41.8%in 2020;including cholecystectomy(40.1%decrease)and pancreas(111.1%decrease).Surgical volumes also decreased by 18.7%in 2020;device-assisted laparoscopic and robot-assisted procedures reduced by 45.4%and 61.9%during the COVID-19 Lockdown in 2020.

In vitro neuroprotective potentials of aqueous and methanol extracts from Heinsia crinita leaves

This study was designed to determine the neuroprotective potentials of aqueous and methanol extracts from Heinsia crinita leaves in vitro.The total phenol and flavonoid contents of the extracts were determined using colorimetric method while phenolic characterization of the leaf was analyzed via high performance liquid chromatography-diode array detector(HPLC-DAD).The effects of the extracts on Fe^2+-induced lipid peroxidation in rats’brain homogenate,monoamine oxidase(MAO),Na^+/K^+-ATPase,acetylcholinesterase(AChE)and butyrylcholinesterase(BChE)activities were also assessed.The aqueous extract had higher total phenol and flavonoid contents than the methanol extract.HPLC-DAD revealed that quercetin ellagic,chlorogenic and caffeic acids were the most abundant phenolic compounds in the leaves.The aqueous extract had higher inhibitory effects on MAO,AChE and BChE activities while there was no significant difference between their Fe^2+-induced lipid peroxidation inhibitory effects.Furthermore,both extracts stimulated Na^+/K^+-ATPase activity;however,methanol extract had higher stimulatory effect.The neuroprotective properties of H.crinita leaves could be associated with its inhibitory effects on Fe2+-induced lipid peroxidation and modulation of MAO,Na^+/K^+-ATPase,AChE,and BChE activities.Therefore,H.crinita leaves could be used as a functional food and dietary intervention for the management of some neurodegenerative diseases.Nevertheless,the aqueous extracts exhibited better neuroprotective properties.

Pros and Cons in Therapeutic Evaluation of Paraoxonase 1 in Nerve Agent Toxicity

PON 1 （Paraoxonase 1） has been proposed as an efficient catalytic bioscavenger to combat against OP （organophosphate） and CWNA （chemical warfare nerve agent） toxicity. Unlike stoichiometric bioscavengers such as butyrylcholinesterase, catalytic bioscavengers are cost effective with the advantage of eliminating all the OPs/CWNAs at low doses. Analysis of catalytic bioscavenger efficacy of PONI showed promising results by various group of researchers. Still, there are large numbers of grey areas which are not addressed so far. One of the major areas of interest is the pharmacokinetic analysis of infused PON 1 in multiple animal models. It is shown that previous studies in mice significantly increased half-life of PONI, while recent studies in guinea pigs from our group showed reduced half-life of PON1. Similar results were reported by other research groups in guinea pigs and non-human primates. The short half-life of exogenously administered PON1 in multiple animal models may be due to poor association of PON1 with its endogenous carrier, high density lipoprotein or lower doses of PON 1 or a reflection of species difference. These observations warrant the significance of thorough pharmacokinetic analysis of infused PON 1 and the development of alternative approaches for successful utility of PON 1 as an efficient medical countermeasure against OP/CWNA toxicity.

Role of Soluble Factors in Immune and Normal Sera in the Control of Giardiasis Due to Giardia Iamblia

Hyperimmune sera (HIS), raised against crude giardia antigen, on in vitro interaction, caused more agglutination of Giardia lamblia trophozoites. Heat inactivated HIS possessed a comparable agglutinating activity as the non-inactivated controls. Non-inactivated normal (unimmunized) serum caused immobilization of Giardia trophozoite, which was checked on heat inactivation. Antibodies in immune sera are mainly responsible for agglutination, whereas the heat labile non-immune components control the mobility of the intestinal parasite.

A bibliometric analysis of global research output on health and human rights(1900–2017)

Background:Baseline data on global research activity on health and human rights(HHR)needs to be assessed and analyzed to identify research gaps and to prioritize funding and research agendas.Therefore,the aim of this study was to assess the growth of publications and research pattern on HHR.Methods:A bibliometric methodology was used.Literature on HHR was retrieved using SciVerse Scopus for the study period from 1900 to 2017.Nine different search scenarios with different keyword combinations were used to retrieve the required documents.All types of documents published in peer-reviewed journals,including editorials,were included.The search strategy was validated.Results:In total 6513 documents were retrieved with an h-index of 88 and an average of 9.8 citations per document.Publications on HHR field started as early as 1950 but showed a steep rise in the past two decades.Visualization of author keywords revealed that HIV/AIDS,mental health,maternal and reproductive health,violence,ethics,torture,and refugees were most commonly encountered keywords.The journal“Health and Human Rights”was most active(n=467;7.2%)in this field.However,documents that appeared in The Lancet received the highest impact(29.5 citations per document).The United States of America produced the most in this field(n=1817;27.9%).Researchers in the region of Americas participated in approximately 45%of the retrieved documents while researchers in the Eastern Mediterranean region had the least contribution(2.5%).Researchers in high-income countries contributed to approximately 78%of the retrieved documents while researchers in low-income countries contributed to less than 5%of the retrieved documents.When data were standardized by population size,the research output from high-income countries was approximately four documents per one million inhabitants.For middle-income countries,the research output was 0.3 document per one million inhabitants.For low-income countries,the research output was 0.5 document per one million inhabitants.Conclusions:Differential research productivity on HHR was seen among scholars in different world regions.World countries need to encourage and strengthen research on HHR in order to achieve the goals set in international agreements of human rights.

Role of complex organic arsenicals in food in aggregate exposure to arsenic

For much of the world＇s population, food is the major source of exposure to arsenic.Exposure to this non-essential metalloid at relatively low levels may be linked to a wide range of adverse health effects. Thus, evaluating foods as sources of exposure to arsenic is important in assessing risk and developing strategies that protect public health. Although most emphasis has been placed on inorganic arsenic as human carcinogen and toxicant, an array of arsenic-containing species are found in plants and animals used as foods. Here,we 2evaluate the contribution of complex organic arsenicals（arsenosugars, arsenolipids,and trimethylarsonium compounds） that are found in foods and consider their origins,metabolism, and potential toxicity. Commonalities in the metabolism of arsenosugars and arsenolipids lead to the production of di-methylated arsenicals which are known to exert many toxic effects. Evaluating foods as sources of exposure to these complex organic arsenicals and understanding the formation of reactive metabolites may be critical in assessing their contribution to aggregate exposure to arsenic.

In vitro and in vivo anticancer potential and molecular targets of the new colchicine analog ⅢM-067

Objective: The current study evaluated various new colchicine analogs for their anticancer activity and to study the primary mechanism of apoptosis and in vivo antitumor activity of the analogs with selective anticancer properties and minimal toxicity to normal cells.Methods: Sulforhodamine B(SRB) assay was used to screen various colchicine analogs for their in vitro cytotoxicity. The effect of N-[(7S)-1,2,3-trimethoxy-9-oxo-10-(pyrrolidine-1-yl)5,6,7,9-tetrahydrobenzo[a] heptalene-7-yl] acetamide(ⅢM-067) on clonogenicity, apoptotic induction, and invasiveness of A549 cells was determined using a clonogenic assay, scratch assay, and staining with 4’,6-diamidino-2-phenylindole(DAPI) and annexin V/propidium iodide. Mitochondrial membrane potential(MMP) and reactive oxygen species(ROS) levels were observed using fluorescence microscopy. Western blot analysis was used to quantify expression of proteins involved in apoptosis, cell cycle, and phosphatidylinositol 3-kinase(PI3K)/protein kinase B(AKT)/mammalian target of rapamycin(mTOR) signaling. Pharmacokinetic and in vivo efficacy studies against Ehrlich ascites carcinoma(EAC) and Ehrlich solid tumor models were conducted using Swiss albino mice.Results: ⅢM-067 showed potent cytotoxicity and better selectivity than all other colchicine analogs screened in this study. The selective activity of ⅢM-067 toward A549 cells was higher among other cancer cell lines,with a selectivity index(SI) value of 2.28. ⅢM-067 demonstrated concentration-and time-dependent cytotoxicity against A549 cells with half-maximal inhibitory concentration values of 0.207, 0.150 and0.106 μmol/L at 24, 48 and 72 h, respectively. It also had reduced toxicity to normal cells(SI > 1) than the parent compound colchicine(SI = 1). ⅢM-067 reduced the clonogenic ability of A549 cells in a dose-dependent manner. ⅢM-067 enhanced ROS production from 24.6% at 0.05 μmol/L to 82.1% at 0.4 μmol/L and substantially decreased the MMP(100% in control to 5.6% at 0.4 μmol/L). The annexin V-FITC assay demonstrated78% apoptosis at 0.4 μmol/L. ⅢM-067 significantly(P < 0.5) induced the expression of various intrinsic apoptotic pathway proteins, and it differentially regulated the PI3K/AKT/mTOR signaling pathway. Furthermore,ⅢM-067 exhibited remarkable in vivo anticancer activity against the murine EAC model, with tumor growth inhibition(TGI) of 67.0% at a dose of 6 mg/kg(i.p.) and a reduced mortality compared to colchicine. ⅢM-067also effectively inhibited the tumor growth in the murine solid tumor model with TGI rates of 48.10%, 55.68%and 44.00% at doses of 5 mg/kg(i.p.), 6 mg/kg(i.p.) and 7 mg/kg(p.o.), respectively.Conclusion: ⅢM-067 exhibited significant anticancer activity with reduced toxicity both in vitro and in vivo and is a promising anticancer candidate. However, further studies are required in clinical settings to fully understand its potential.

Allium cepa root tip assay in assessment of toxicity of magnesium oxide nanoparticles and microparticles

Allium cepa bioassay had been used from decades for the assessment of toxicants and their harmful effects on environment as well as human health. Magnesium oxide（MgO） particles are being utilized in different fields. However, reports on the adverse effects of MgO nanoparticles on the environment and mankind are scarce. Hence, the toxicity of MgO particles is of concern because of their increased utilization. In the current study, A. cepa was used as an indicator to assess the toxicological efficiency of MgO nano-and microparticles（NPs and MPs） at a range of exposure concentrations（12.5, 25, 50, and100 μg/m L）. The toxicity was evaluated by using various bioassays on A. cepa root tip cells such as comet assay, oxidative stress and their uptake/internalization profile. Results indicated a dose dependent increase in chromosomal aberrations and decrease in mitotic index（MI） when compared to control cells and the effect was more significant for NPs than MPs（at p 〈 0.05）. Comet analysis revealed that the Deoxyribonucleic acid（DNA） damage in terms of percent tail DNA ranged from 6.8–30.1 over 12.5–100 μg/m L concentrations of MgO NPs and was found to be significant at the exposed concentrations. A significant increase in generation of hydrogen peroxide and superoxide radicals was observed in accordance with the lipid peroxidation profile in both MgO NPs and MPs treated plants when compared with control. In conclusion, this investigation revealed that MgO NPs exposure exhibited greater toxicity on A. cepa than MPs.

Bisphenol A exposure alters release of immune and developmental modulators and expression of estrogen receptors in human fetal lung fibroblasts

Bisphenol A （BPA） has been shown to exert biological effects through estrogen receptor （ER）-dependent and ER-independent mechanisms. Recent studies suggest that prenatal exposure to BPA may increase the risk of childhood asthma. To investigate the underlying mechanisms in the actions of BPA, human fetal lung fibroblasts {hFLFs） were exposed to varying doses of BPA in culture for 24 hr. Effects of BPA on localization and uptake of BPA, cell viability, release of immune and developmental modulators, cellular localization and expression of ERa, ERβ and G-protein coupled estrogen receptor 30 （GPR30）, and effects of ERs antagonists on BPA-induced changes in endothelin-1 （ET-1） release were examined. BPA at 0.01-100 μmol/L caused no changes in cell viability after 24 hr of exposure, hFLFs expresses all three ERs. BPA had no effects on either cellular distribution or protein expression of ERa, however, at 100 μmol/L （or 23 μmol/L intracellular BPA） increased ERβ protein levels in the cytoplasmic fractions and GPR30 protein levels in the nuclear fractions. These paralleled with increased release of growth differentiation factor-15, decreased phosphorylation of nuclear factor kappa B p65 at serine 536, and decreased release of ET-1, interleukin-6, and interferon gamma-induced protein 10. ERs antagonists had no effects on BPA-induced decrease in ET-1 release. These data suggest that BPA at 100 μmol/L altered the release of immune and developmental modulators in hFLFs, which may negatively influence fetal lung development, maturation, and susceptibility to environmental stressors, although the role of BPA in childhood asthma remains to be confirmed in in viuo studies.

Ethanol Extract of Phellinus merrillii Protects against Diethylnitrosamine- and 2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Rats

Objective： To study whether the ethanol extract of Phellinus merrillii（EPM） has chemopreventive potential against liver carcinogenesis. Methods： Thirty male Spraque-Dawley rats were randomly divided into control group, EPM control group, hepatocarcinoma control group, low-dose EPM group and high-dose EPM group, 6 in each group. Using the Solt and Farber protocol in a rat model of hepatocarcinogenesis, the chemopreventive effect of EPM on diethylnitrosamine（DEN）-initiated, 2-acetylaminofluorene（2-AAF） and partial hepatectomy（PH）-promoted liver carcinogenesis in rats was evaluated. Basic pathophysiological and histological examinations, together with the serum levels of glutamic oxaloacetic transaminase（s GOT）, glutamic pyruvic transaminase（s GPT） and gamma-glutamyl transpeptidase（γ-GT） were measured. Results： Treatment of EPM at the concentration of 2 g/kg body weight in the diet for 8 weeks clearly prevented the development of carcinogenesis and reduced the levels of s GOT, s GPT, and serum γ-GT of rats as compared with the hepatocarcinoma control group（P〈0.05 or P〈0.01）. These phenotypes were accompanied by a significant increase in natural killer cell activity. Conclusion： EPM showed a strong liver preventive effect against DEN＋2-AAF＋PH-induced hepatocarcinogenesis in a rat model.

Global output of research on epidermal parasitic skin diseases from 1967 to 2017

Background:Epidermal parasitic skin diseases(EPSD)occur in most countries and cause a considerable health and economic burden,particularly in the tropics and subtropics.The aim of this study was to assess and analyse peerreviewed literature on EPSD in humans.The results of this study serve as an indicator of the extent the scientific community,health authorities,and international health agencies interact with EPSD as a health problem that is commonly associated with poverty and poor hygiene.Methods:A bibliometric analysis methodology was used.The Scopus database was used to retrieve documents about EPSD for the study period(1967-2017).The study focused on scabies,tungiasis,pediculosis,hookwormrelated cutaneous larva migrans(HrCLM),myiasis,and cutaneous strongyloidiasis.Documents that specifically and explicitly discuss EPSD in animals,aquatic organisms,and birds were excluded.Results:In total,4186 documents were retrieved.A fluctuated growth of publications on EPSD in the past five decades was found.The retrieved documents received 43301 citations,an average of 10.3 citations per article and an h-index of 74.The keywords“scabies”and was the most commonly encountered keyword followed by the keywords“head lice”and“pediculosis”.The most active journal involved in publishing articles on EPSD was the International Journal of Dermatology(164;3.9%).Researchers from 93 different countries published the retrieved articles.The USA led with 735(17.6%)documents,followed by the UK(274;6.5%),and Germany(259;6.2%).In terms of institutions,the Charite-Universitätsmedizin Berlin in Germany was the most active in this field with 78(1.9%)publications,followed by the Universidade Federal do Cearáin Brazil with 52(1.2%)publications.Conclusions:Research on scabies and pediculosis dominated the field of EPSD research to the expense of tungiasis,HrCLM,myiasis,and cutaneous strongyloidiasis.There was an underrepresentation of literature from the tropics and subtropics despite EPSD being common in these areas.This could possibly be explained by the presence of limited number of non-English journals in the Scopus database.International research collaborations and research networking should be strengthened to help advance and prioritize research on EPSD.

Effects of sulforaphane on brain mitochondria: mechanistic view and future directions

The organosulfur compound sulforaphane(SFN;C6H11NOS2) is a potent cytoprotective agent promoting antioxidant, anti-inflammatory, antiglycative, and antimicrobial effects in in vitro and in vivo experimental models. Mitochondria are the major site of adenosine triphosphate(ATP) production due to the work of the oxidative phosphorylation(OXPHOS) system. They are also the main site of reactive oxygen species(ROS) production in nucleated human cells. Mitochondrial impairment is central in several human diseases, including neurodegeneration and metabolic disorders. In this paper, we describe and discuss the effects and mechanisms of action by which SFN modulates mitochondrial function and dynamics in mammalian cells. Mitochondria-related pro-apoptotic effects promoted by SFN in tumor cells are also discussed. SFN may be considered a cytoprotective agent, at least in part, because of the effects this organosulfur agent induces in mitochondria. Nonetheless, there are certain points that should be addressed in further experiments, indicated here as future directions, which may help researchers in this field of research.