Anita Mandal

Mechanisms of heavy-metal sequestration and detoxification in crustaceans: a review.

This review is an update of information recently obtained about the physiological, cellular, and molecular mechanisms used by crustacean organ systems to regulate and detoxify environmental heavy metals. It uses the American lobster, Homarus americanus, and other decapod crustaceans as model organisms whose cellular detoxification processes may be widespread among both invertebrates and vertebrates alike. The focus of this review is the decapod hepatopancreas and its complement of metallothioneins, membrane metal transport proteins, and vacuolar sequestration mechanisms, although comparative remarks about potential detoxifying roles of gills, integument, and kidneys are included. Information is presented about the individual roles of hepatopancreatic mitochondria, lysosomes, and endoplasmic reticula in metal sequestration and detoxification. Current working models for the involvement of mitochondrial and endoplasmic reticulum calcium-transport proteins in metal removal from the cytoplasm and the inhibitory interactions between the metals and calcium are included. In addition, copper transport proteins and V-ATPases associated with lysosomal membranes are suggested as possible sequestration processes in these organelles. Together with several possible cytoplasmic divalent and trivalent anions such as sulfate, oxalate, or phosphate, accumulations of metals in lysosomes and their complexation into detoxifying precipitation granules may be regulated by variations in lysosomal pH brought about by bafilomycin-sensitive proton ATPases. Efflux processes for metal transport from hepatopancreatic epithelial cells to the hemolymph are described, as are the possible roles of hemocytes as metal sinks. While some of the cellular processes for isolating heavy metals from general circulation occur in the hepatopancreas and are beginning to be understood, very little is currently known about the roles of the gills, integument, and kidneys in metal regulation. Therefore, much remains to be clarified about the organs and mechanisms involved in metal homeostasis in decapod crustaceans.

Expression of Na+/d-glucose cotransport in Xenopus laevis oocytes by injection of poly(A)+ RNA isolated from lobster (Homarus americanus) hepatopancreas

Xenopus laevis oocytes were used for expression and characterization of lobster (Homarus americanus) hepatopancreas Na(+)-dependent D-glucose transport activity. Poly(A)(+) RNA from the whole hepatopancreatic tissue was injected and transport activity was assayed by alpha-D-[2-(3)H] glucose. Injection of lobster hepatopancreatic poly(A)(+) RNA resulted in a dose (1-20 ng) and time (1-5 days) dependent increase of Na(+)-dependent D-glucose uptake. Kinetics of Na(+)-dependent glucose transport was a hyperbolic function (K(m)=0.47+/-0.04 mM) of external D-glucose concentration and a sigmoidal function (K(Na)=68.32+/-1.57 mM; Hill coefficient=2.22+/-0.09) of external Na(+) concentration. In addition, Na(+)-dependent D-glucose uptake was significantly inhibited by both (0.1-0.5 mM) phloridzin and (0.1-0.5 mM) methyl-alpha-D-glucopyranoside. After size fractionation through a sucrose density gradient, poly(A)(+) RNA fractions with an average length of 2-4 kb induced a twofold increase in Na(+)-dependent phloridzin-inhibited D-glucose uptake as compared to total poly(A)(+) RNA-induced uptake. The results of this study provide the functional basis to screen lobster hepatopancreatic cDNA libraries for clones encoding putative and still not known crustacean SGLT-type Na(+)/glucose co-transporter(s).

Infant Mortality: A Leading Health Indicator

The purpose of this research was to study infant mortality and their rates in Duval County, Florida. Infant mortality rate is the estimate of infant deaths per 1,000 live births. The U.S. Infant Mortality Rate (IMR) currently ranks 27th among industrialized countries, with wide and persistent disparities by race, socioeconomic status, and geography. The objective of this research was to study infant mortality rates in each zip code in Duval County along with demographic information such as poverty, household income, prenatal care, and education. An analysis of the data collected was then used to establish whether there is a correlation between as poverty, household income, prenatal care, and education with infant mortality rates in zip codes with the highest and lowest infant mortality rates. The data for this research was gathered through the Florida Health department and nefloridacounts.org. The infant mortality rates and demographic information was sourced from the year 2014.

Community-Based Educational Approach to Reduce Health Disparity

Health disparities refer to differences between groups of people. These differences can affect how frequently a disease affects a group, how many people get sick, or how often the disease cause death. Racial and ethnic disparities in health and health care recently have received considerable attention. Racial and ethnic minorities tend to receive poorer quality care compared with non-minorities. The Institute of Medicine (IOM) defines disparities as “racial or ethnic differences in the quality of health care that are not due to access-related factors or clinical needs, preferences, and appropriateness of intervention [1]. While the World Health Organization (WHO), have adopted a different view of what constitutes a disparity, major stakeholders agree that such disparities are unjust and need to be addressed [2]. In order to decrease this differential, it is critical to understand the particular barriers to health and health care that underserved minorities face. The barriers have been identified as: inadequate access to and availability of health care services, lack of knowledge of disease prevention and screening recommendations, low literacy, mistrust of the health care system, fear, fatalism regarding cure, genetic and environmental risk factors.

Molecular Biomarkers: Tools of Medicine

Molecular biomarkers are emerging as the key indices for the management of patients with significant diseases. Motivated by the systematic effort to define the human genome, the creation of rapid analytic technologies for evaluating nucleic acids and proteins has provided the technological “boom” for the development of molecular biomarkers. Collaboration and cooperation between stakeholders involved in biomarker development, application, and regulation may be the most expeditious route toward the translation of laboratory discovery into patient management. In summary, intensive research has originated multiple factors or biomarkers that are likely to be helpful in diagnosis, characterization, and therapy selection of different patients. A thorough understanding of the relevance of each biomarker will be the key to efficiently diagnose a disease and direct the patients towards the drugs more likely to be of benefit based on their particular profile. The papers selected for this special issue represent an excellent panel for addressing the molecular biomarkers as the future tools of medicine. This special issue contains thirteen papers. In the paper entitled “Circulating microRNAs and kallikreins before and after radical prostatectomy: are they really prostate cancer markers?,” M. G. Egidi et al. presented 38 patients with prostate cancer. They suggested that two miRNAs (miR-21 and miR-141) could be involved in post surgical inflammatory processes. Postoperative serum kallikreins showed a significant decrease, highlighting the potential usefulness of kallikreins apart from PSA as potential prostate cancer markers. In the paper entitled “A novel differential predict model based on matrixx-assisted laser ionization time of flight mass spectrometry and serum ferritin for acute graft-versus-host disease,”. C.-Y. Zhang et al. investigated the possibility of pre warning the risk of an acute graft-versus-host disease (aGVHD) before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT) by serum profiling combining with serum ferritinin. Their joint prewarning model could predict the risk of aGVHD, especially severe aGVHD before transplant which provide a reliable method to continuously monitor the condition of patients. In the paper entitled “The use of multidimensional data to identify the molecular biomarker for pancreatic ductal adenocarcinoma,” L. Zhuang et al. presented that they have adopted an integrative approach to simultaneously identify biomarker and generate testable hypothesis from multidimensional omics data. They have found that PER2 expression was highly associated with the survival data, thus representing a novel biomarker for earlier detection of pancreatic ductal adenocarcinoma (PDAC). In the paper entitled “Clinical evaluation and cost-effectiveness analysis of serum tumor markers in lung cancer,” R. Wang et al. showed that combinations of four tumor markers (SCCA, NSE, CEA, and CYFRA21-1) improved the sensitivity for lung cancer and different combination panels had their own usefulness. NSE, CEA, and CYFRA21-1 were the optimal combination panel with highest Youdens index (0.64), higher sensitivity (75.76%), and specificity (88.57%), which can aid in clinical diagnosis of lung cancer. In the paper entitled “Immune parameters in the prognosis and therapy monitoring of cutaneous melanoma patients: experience, role, and limitations,” M. Neagu et al. reported the follow-up for 36 months of the immune parameters of patients diagnosed in stages I–IV, namely, pre- and postsurgery immune circulating peripheral cells and circulating intercommunicating cytokines. In the paper entitled “Comparative gene expression profiling in human cumulus cells according to ovarian gonadotropin treatments,” S. Assou et al. provided an exclusive study characterizing gene expression profiles in cumulus cells (CCs) of periovulatory follicles from patients undergoing HP-hMG and rFSH gonadotropin treatments during in vitro fertilization cycles. This project has characterized the expression of these genes as biomarkers of in vitro embryo quality. In the paper entitled “Aptamers: novel molecules as diagnostic markers in bacterial and viral infections?,” F. M. Zimbres et al. urged an urgent need to discover novel diagnostic as well as therapeutic tools against infectious agents. They viewed that the systematic evolution of ligands by exponential enrichment (SELEX) represents a powerful technology to target selective pathogenic factors as well as entire bacteria or viruses. SELEX uses a large combinatorial oligonucleic acid library (DNA or RNA) which is processed by a high-flux in vitro screen of iterative cycles. In the paper entitled “Distribution of ABO blood group and major cardiovascular risk factors with coronary heart disease,” S. Biswas et al. viewed that the AB blood group decreases the risk of CHD in healthy controls; it might be due to the higher concentration of high density lipoprotein cholesterol (HDL-c), while the O blood group increases the risk of CHD due to lower HDL-c levels in Bengali population of eastern part of India. In the paper entitled “Immunomodulatory effect of continuous veno-venous hemofiltration during sepsis: preliminary data,” G. Servillo et al. reported that severe sepsis and septic shock are the primary causes of multiple organ dysfunction syndrome (MODS), which is the most frequent cause of death in intensive care unit patients. Many pro- and anti-inflammatory mediators, such as interleukin-6 (IL-6), play a key role in septic syndrome. Continuous renal replacement therapy (CRRT) removes in a nonselective way pro- and anti-inflammatory mediators. The authors investigate the effects of continuous venovenous hemofiltration (CVVH) as immunomodulatory treatment of sepsis in a prospective clinical study. In the paper entitled “Acetylcholinesterase as biomarker in environmental and occupational medicine: new insights and future perspectives,” M. G. Lionetto et al. viewed that Acetylcholinesterase (AChE) is a key enzyme in the nervous system (NS), since it terminates nerve impulses by catalyzing the hydrolysis of acetylcholine. As a specific molecular target of organophosphate and carbamate pesticides, AChE activity and inhibition are a human biological marker of pesticide poisoning. Thus, it is used to study the effects of the exposure to organophosphate and carbamate pesticides on NS in occupational and environmental medicine. This paper reviews and discusses the recent findings about AChE, including its sensitivity to other pollutants and expression of different splice variants. These insights open new perspectives for the use of this biomarker in environmental and occupational human health monitoring. In the paper entitled “Polyisoprenylated methylated protein methyl esterase is both sensitive to curcumin and overexpressed in colorectal cancer: implications for chemoprevention and treatment,” F. Amissah et al. discussed polyisoprenylated methylated protein methyl esterase (PMPMEase) which cocatalyzes the polyisoprenylation pathway required to process various monomeric G proteins. Mutation of these G proteins is considered to be responsible for 50% of colorectal cancers. This interesting finding suggests that elevated PMPMEase activity and its overexpression can be one of the candidate markers for early diagnosis of colorectal cancer. Susceptibility of this enzyme to curcumin also suggests that PMPMEase can be a potential candidate for targeted anticancer therapy. In the paper, entitled “Emerging therapeutic biomarkers in endometrial cancer,” P. Dong et al. reviewed the current status of molecular therapies tested in clinical trials and mainly discussed the potential therapeutic candidates that are possibly used to develop more effective and specific therapies against endometrial cancer progression and metastasis. In the paper entitled “Mouse prostate epithelial luminal cells lineages originate in the basal layer where the primitive stem/early progenitor cells reside: implications for identifying prostate cancer stem cells” J. Zhou et al. have developed an in vivo cell fate tracing mouse model and an in vivo slow-cycling cell label mouse model to provide further insight into this question. Through genetic manipulation in the animals, their findings indicate that the basal cell lineage can produce more differentiated luminal cells; the putative mouse prostate stem cells (which are slow-cycling and responsible for tissue maintenance) likely reside in the basal layer. Though the selected topics and papers are not an exhaustive representation of the entire area of molecular biomarkers and tools of medicine, yet they represent the rich and many-faceted knowledge that we have the privilege of sharing with the readers.