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MSystems Jun 2024spp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and...
spp. are renowned for producing the hepatotoxin microcystin in freshwater cyanobacterial harmful algal blooms around the world, threatening drinking water supplies and public and environmental health. However, genomes also harbor numerous biosynthetic gene clusters (BGCs) encoding the biosynthesis of other secondary metabolites, including many with toxic properties. Most of these BGCs are uncharacterized and currently lack links to biosynthesis products. However, recent field studies show that many of these BGCs are abundant and transcriptionally active in natural communities, suggesting potentially important yet unknown roles in bloom ecology and water quality. Here, we analyzed 21 xenic cultures isolated from western Lake Erie to investigate the diversity of the biosynthetic potential of this genus. Through metabologenomic and approaches, we show that these strains contain variable BGCs, previously observed in natural populations, and encode distinct metabolomes across cultures. Additionally, we find that the majority of metabolites and gene clusters are uncharacterized, highlighting our limited understanding of the chemical repertoire of spp. Due to the complex metabolomes observed in culture, which contain a wealth of diverse congeners as well as unknown metabolites, these results underscore the need to deeply explore and identify secondary metabolites produced by beyond microcystins to assess their impacts on human and environmental health.IMPORTANCEThe genus forms dense cyanobacterial harmful algal blooms (cyanoHABs) and can produce the toxin microcystin, which has been responsible for drinking water crises around the world. While microcystins are of great concern, also produces an abundance of other secondary metabolites that may be of interest due to their potential for toxicity, ecological importance, or pharmaceutical applications. In this study, we combine genomic and metabolomic approaches to study the genes responsible for the biosynthesis of secondary metabolites as well as the chemical diversity of produced metabolites in strains from the Western Lake Erie Culture Collection. This unique collection comprises strains that were directly isolated from western Lake Erie, which experiences substantial cyanoHAB events annually and has had negative impacts on drinking water, tourism, and industry.
PubMed: 38916306
DOI: 10.1128/msystems.00334-24 -
Drug Design, Development and Therapy 2024Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether...
Short-Term Preconditioning with Insulin and Glucose Efficiently Protected the Kidney Against Ischemia-Reperfusion Injury via the P-AKT-Bax-Caspase-3 Signaling Pathway in Mice.
OBJECTIVE
Insulin attaches insulin receptor to activate the PI3-kinase/Akt signaling to maintain glucose homeostasis and inhibit apoptosis. This study determined whether preconditioning with insulin and glucose protects the kidney against ischemia-reperfusion injury (IRI).
METHODS
Kidney IRI was performed in C57BL/6 mice by clamping the renal vessels for 30 min, followed by reperfusion for 24 h. A total subcutaneous 0.1 unit of insulin along with 10% glucose in drinking water was treated on the mice for 24 h before kidney IRI. The kidney function and injuries were investigated through the determination of BUN and Cr in blood plasma, as well as the apoptosis and the expression of P-AKT, BAX, and caspase-3 in the kidneys. The role of P-AKT in insulin-treated IRI kidneys was tested using an AKT inhibitor. The effects of the preconditional duration of insulin and glucose on IRI kidneys were investigated by expanding the treatment duration to 1, 3, and 6 days.
RESULTS
Preconditioning with insulin and glucose protected the kidney against IRI as manifested by a decrease in creatinine and BUN and a reduction of kidney tubular injury. The protection effect was mediated by P-AKT-BAX-caspase-3 signaling pathway resulting in suppression of apoptotic cell death. An AKT inhibitor partially reversed the protective effects of preconditional insulin. The preconditional duration for 1, 3, and 6 days had no differences in improving kidney functions and pathology.
CONCLUSION
A short-term preconditioning with insulin and glucose protected the kidney from IRI through the activation of p-AKT and subsequent reduction of BAX-caspase-3-induced apoptosis. The short-term precondition provides a practicable strategy for protecting the kidney against predictable IRI, such as kidney transplant and major surgical operations with high risk of hypotension.
Topics: Animals; Reperfusion Injury; Proto-Oncogene Proteins c-akt; Mice; Mice, Inbred C57BL; Signal Transduction; Insulin; Male; Caspase 3; Glucose; bcl-2-Associated X Protein; Kidney; Apoptosis
PubMed: 38915866
DOI: 10.2147/DDDT.S465836 -
International Journal of Bipolar... Jun 2024Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of... (Review)
Review
BACKGROUND
Decades of clinical research have demonstrated the efficacy of lithium in treating acute episodes (both manic and depressive), as well as in preventing recurrences of bipolar disorder (BD). Specific to lithium is its antisuicidal effect, which appears to extend beyond its mood-stabilizing properties. Lithium's clinical effectiveness is, to some extent, counterbalanced by its safety and tolerability profile. Indeed, monitoring of lithium levels is required by its narrow therapeutic index. There is consensus that adequate serum levels should be above 0.6 mEq/L to achieve clinical effectiveness. However, few data support the choice of this threshold, and increasing evidence suggests that lithium might have clinical and molecular effects at much lower concentrations.
CONTENT
This narrative review is aimed at: (1) reviewing and critically interpreting the clinical evidence supporting the use of the 0.6 mEq/L threshold, (2) reporting a narrative synthesis of the evidence supporting the notion that lithium might be effective in much lower doses. Among these are epidemiological studies of lithium in water, evidence on the antisuicidal, anti-aggressive, and neuroprotective effects, including efficacy in preventing cognitive impairment progression, Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS), of lithium; and (3) revieweing biological data supporting clinically viable uses of lithium at low levels with the delineation of a mechanistic hypothesis surrounding its purported mechanism of action. The study selection was based on the authors' preference, reflecting the varied and extensive expertise on the review subject, further enriched with an extensive pearl-growing strategy for relevant reviews and book sections.
CONCLUSIONS
Clinical and molecular effects of lithium are numerous, and its effects also appear to have a certain degree of specificity related to the dose administered. In sum, the clinical effects of lithium are maximal for mood stabilisation at concentrations higher than 0.6 mEq/l. However, lower levels may be sufficient for preventing depressive recurrences in older populations of patients, and microdoses could be effective in decreasing suicide risk, especially in patients with BD. Conversely, lithium's ability to counteract cognitive decline appears to be exerted at subtherapeutic doses, possibly corresponding to its molecular neuroprotective effects. Indeed, lithium may reduce inflammation and induce neuroprotection even at doses several folds lower than those commonly used in clinical settings. Nevertheless, findings surrounding its purported mechanism of action are missing, and more research is needed to investigate the molecular targets of low-dose lithium adequately.
PubMed: 38914810
DOI: 10.1186/s40345-024-00345-8 -
Scientific Reports Jun 2024Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the...
Hyperthermia induced by phenethylamines, such as 3,4-methylenedioxymethamphetamine (MDMA), can lead to life-threatening complications and death. Activation of the sympathetic nervous system and subsequent release of norepinephrine and activation of uncoupling proteins have been demonstrated to be the key mediators of phenethylamine-induced hyperthermia (PIH). Recently, the gut microbiome was shown to also play a contributing role in PIH. Here, the hypothesis that bile acids (BAs) produced by the gut microbiome are essential to PIH was tested. Changes in the serum concentrations of unconjugated primary BAs cholic acid (CA) and chenodeoxycholic acid (CDCA) and secondary BA deoxycholic acid (DCA) were measured following MDMA (20 mg/kg, sc) treatment in antibiotic treated and control rats. MDMA-induced a significant hyperthermic response and reduced the serum concentrations of three BAs 60 min post-treatment. Pretreatment with antibiotics (vancomycin, bacitracin and neomycin) in the drinking water for five days resulted in the depletion of BAs and a hypothermic response to MDMA. Gut bacterial communities in the antibiotic-treated group were distinct from the MDMA or saline treatment groups, with decreased microbiome diversity and alteration in taxa. Metagenomic functions inferred using the bioinformatic tool PICRUSt2 on 16S rRNA gene sequences indicated that bacterial genes associated to BA metabolism are less abundant in the antibiotic-MDMA treated group. Overall, these findings suggest that gut bacterial produced BAs might play an important role in MDMA-induced hyperthermia.
Topics: Gastrointestinal Microbiome; N-Methyl-3,4-methylenedioxyamphetamine; Animals; Rats; Male; Hyperthermia; Bile Acids and Salts; Anti-Bacterial Agents; Rats, Sprague-Dawley; RNA, Ribosomal, 16S; Deoxycholic Acid
PubMed: 38914648
DOI: 10.1038/s41598-024-65433-2 -
Scientific Reports Jun 2024Lakes are a crucial source of drinking water, provide ecological services from fisheries and aquaculture to tourism and are also a critical part of the global carbon...
Lakes are a crucial source of drinking water, provide ecological services from fisheries and aquaculture to tourism and are also a critical part of the global carbon cycle. Therefore, it is important to understand how lakes are changing over time. The ESA Ocean Colour Climate Change Initiative (OC-CCI) database allows to study changes in the largest lakes over 1997-2023 period. The Caspian Sea and ten next largest lakes were under investigation. Changes in the phytoplankton biomass (Chl-a), the concentration of particulate matter (b(555)), the colored dissolved organic matter, CDOM (a(412)), and the light diffuse attenuation coefficient in water (K(490)) were analyzed. Both increasing and decreasing trends (or no significant trend at all) of studied parameters were observed in these lakes over the study period. In some of the Laurentian Great Lakes the changes in CDOM over the study period were found to be in accordance with the lake water level changes i.e. with the inflow from the catchment. There was difference between the trends of Chl-a and b(555) in lakes Michigan and Huron indicating that there may have been shift in phytoplankton community that took place around 2005. The study demonstrated that remote sensing products, like the ones created by ESA OC-CCI, are valuable tools to study behavior of large lakes ecosystems over time.
PubMed: 38909085
DOI: 10.1038/s41598-024-65250-7 -
Environment International Jun 2024Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In...
Emerging evidence has linked arsenic exposure and metabolic homeostasis, but the mechanism is incompletely understood, especially at relatively low concentrations. In this study, we used a mouse model to evaluate the health impacts and metabolic toxicity of arsenic exposure in drinking water at environmentally relevant levels (0.25 and 1.0 ppm). Our results indicated that arsenic damaged intestinal barrier and induced arsenic accumulation, oxidative stress, and pathological changes in the liver and illum. Interestingly, arsenic increased the hepatic triglyceride (TG) and total cholesterol (TC), while reduced serum TG and TC levels. The liver transcriptome found that arsenic exposure caused transcriptome perturbation and promoted hepatic lipid accumulation by regulating the exogenous fatty acids degradation and apolipoproteins related genes. The serum metabolomics identified 74 and 88 differential metabolites in 0.25 and 1.0 ppm, respectively. The KEGG disease and subcellular location analysis indicated that arsenic induced liver and intestinal diseases, and the mitochondrion might be the target organelle for arsenic-induced toxicity. Co-enrichment of transcriptome and metabolome identified 24 metabolites and 9 genes as metabolic toxicity biomarkers. Moreover, 40 male (20 nonalcoholic fatty liver disease (NAFLD) cases and 20 healthy controls) was further selected to validate our findings. Importantly, the significantly changed L-palmitoylcarnitine, 3-hydroxybutyric acid, 2-hydroxycaproic acid and 6 genes of Hadha, Acadl, Aldh3a2, Cpt1a, Cpt2, and Acox1 were found in the NAFLD cases. The results from integrated multi-omics and chemical-protein network analysis indicated that L-palmitoylcarnitine played a critical role in metabolic toxicity by regulating mitochondrial fatty acids β-oxidation genes (Cpt1a, Cpt2). In conclusion, these findings provided new clues for the metabolic toxicity of arsenic exposure at environmentally relevant levels, which involved in the late-life NAFLD development. Our results also contribute to understanding the human responses and phenotypic changes to this hazardous material exposure in the environment.
PubMed: 38906090
DOI: 10.1016/j.envint.2024.108819 -
Animal : An International Journal of... May 2024Dairy cows may suffer thermal stress during the colder seasons especially due to their open-air housing systems. Free water temperature (FWT) and feed temperature (FT)...
Dairy cows may suffer thermal stress during the colder seasons especially due to their open-air housing systems. Free water temperature (FWT) and feed temperature (FT) are dependent on ambient temperature (AT) and can be critical for maintaining body and reticulorumen temperature (RT) in cold conditions. The objective of this study was to determine the effects of FWT and FT on RT fluctuations, and of AT on RT and drinking and eating behaviors in late-lactation cows during cold exposure. Data were collected from 16 multiparous lactating cows for four 6-d periods during the autumn and winter seasons. The cows (224 ± 36 days in milk; mean ± SD) had an average milk yield (MY) of 24.8 ± 4.97 kg/d and RT of 38.84 ± 0.163 °C. Daily average AT ranged from 4.38 to 17.25 °C. The effects of the temperature and amount of the ingested water or feed on RT change and recovery time, and the effect of the daily AT on RT, feed and water intake, and drinking, eating, and rumination behaviors were analyzed using the generalized additive mixed model framework. Reticulorumen temperature change and recovery time were affected by FWT (+0.0596 °C/°C and -1.27 min/°C, respectively), but not by FT. The amount of the ingested free water and feed affected RT change (-0.108 °C/kg drink size and -0.150 °C/kg meal size, respectively), and RT recovery time (+2.13 min/kg drink size and + 3.71 min/kg meal size, respectively). Colder AT decreased RT by 0.0151 °C/°C between 9.91 and 17.25 °C AT. Cows increased DM intake (DMI) by 0.365 kg/d per 1 °C drop in AT below 10.63 °C, but with no increase in MY. In fact, MY:DMI decreased by 0.0106/°C as AT dropped from 17.25 to 4.38 °C. Free water intake (FWI) was reduced by 0.0856 FWI:DMI/°C as AT decreased from 17.25 to 8.27 °C. Cold exposure influenced animal behavior with fewer drink and meal bouts (-0.432 and -0.290 bouts/d, respectively), larger drink sizes (+0.100 kg/bout), and shorter rumination time (-5.31 min/d) per 1 °C decrease in AT from 17.25 °C to 8.77, 12.53, 4.38, and 10.32 °C, respectively. In conclusion, exposure to low AT increased feed intake, reduced water intake, and changes in eating, drinking and rumination behaviors of dairy cows in late lactation. Additionally, the consequences of cold exposure on cows may be aggravated by ingestion of feed and free water at temperatures lower than the body, potentially impacting feed efficiency due to the extra energetic cost of thermoregulation.
PubMed: 38905777
DOI: 10.1016/j.animal.2024.101209 -
Gut Microbes 2024Gut bacteria regulate brain pathology of Alzheimer's disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study,...
Gut bacteria regulate brain pathology of Alzheimer's disease (AD) patients and animal models; however, the underlying mechanism remains unclear. In this study, 3-month-old APP-transgenic female mice with and without knock-out of gene were treated with antibiotics-supplemented or normal drinking water for 2 months. The antibiotic treatment eradicated almost all intestinal bacteria, which led to a reduction in Il-17a-expressing CD4-positive T lymphocytes in the spleen and gut, and to a decrease in bacterial DNA in brain tissue. Depletion of gut bacteria inhibited inflammatory activation in both brain tissue and microglia, lowered cerebral Aβ levels, and promoted transcription of gene in the brain of APP-transgenic mice, all of which effects were abolished by deficiency of Il-17a. As possible mechanisms regulating Aβ pathology, depletion of gut bacteria inhibited β-secretase activity and increased the expression of Abcb1 and Lrp1 in the brain or at the blood-brain barrier, which were also reversed by the absence of Il-17a. Interestingly, a crossbreeding experiment between APP-transgenic mice and knockout mice further showed that deficiency of Il-17a had already increased Abcb1 and Lrp1 expression at the blood-brain barrier. Thus, depletion of gut bacteria attenuates inflammatory activation and amyloid pathology in APP-transgenic mice via Il-17a-involved signaling pathways. Our study contributes to a better understanding of the gut-brain axis in AD pathophysiology and highlights the therapeutic potential of Il-17a inhibition or specific depletion of gut bacteria that stimulate the development of Il-17a-expressing T cells.
Topics: Animals; Alzheimer Disease; Interleukin-17; Gastrointestinal Microbiome; Mice; Mice, Transgenic; Brain; Female; Disease Models, Animal; Mice, Knockout; Amyloid Precursor Protein Secretases; Amyloid beta-Peptides; Anti-Bacterial Agents; Mice, Inbred C57BL; Microglia; CD4-Positive T-Lymphocytes; Blood-Brain Barrier; Humans; Low Density Lipoprotein Receptor-Related Protein-1
PubMed: 38904096
DOI: 10.1080/19490976.2024.2363014 -
International Journal of Public Health 2024This systematic review and meta-analysis aimed to: i) determine the pooled prevalence of acute diarrhea; and ii) synthesize and summarize current evidence on factors of... (Meta-Analysis)
Meta-Analysis Review
This systematic review and meta-analysis aimed to: i) determine the pooled prevalence of acute diarrhea; and ii) synthesize and summarize current evidence on factors of acute diarrheal illnesses among under-five children in Ethiopia. A comprehensive systematic search was conducted in PubMed, SCOPUS, HINARI, Science Direct, Google Scholar, Global Index Medicus, Directory of Open Access Journals (DOAJ), and the Cochrane Library. This systematic review and meta-analysis followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guideline. The methodological quality of each included article was assessed using the Joanna Briggs Institute (JBI) quality assessment tool for cross-sectional and case-control studies. A random-effect meta-analysis model was used to estimate the pooled prevalence of diarrheal illnesses. Heterogeneity and publication bias were assessed using I test statistics and Egger's test, respectively. The statistical analysis was done using STATA™ software version 14. Fifty-three studies covering over 27,458 under-five children who met the inclusion criteria were included. The pooled prevalence of diarrhea among under-five children in Ethiopia was found to be 20.8% (95% CI: 18.69-22.84, n = 44, I = 94.9%, < 0.001). Our analysis revealed a higher prevalence of childhood diarrhea in age groups of 12-23 months 25.42% (95%CI: 21.50-29.35, I = 89.4%, < 0.001). In general, the evidence suggests that diarrheal risk factors could include: i) child level determinants (child's age 0-23 months, not being vaccinated against rotavirus, lack of exclusive breastfeeding, and being an under-nourished child); ii) parental level determinants {mothers poor handwashing practices [pooled odds ratio (OR) = 3.05; 95% CI:2.08-4.54] and a history of maternal recent diarrhea (pooled OR = 3.19, 95%CI: 1.94-5.25)}; and iii) Water, Sanitation and Hygiene (WASH) determinants [lack of toilet facility (pooled OR = 1.56, 95%CI: 1.05-2.33)], lack handwashing facility (pooled OR = 4.16, 95%CI: 2.49-6.95) and not treating drinking water (pooled OR = 2.28, 95% CI: 1.50-3.46). In Ethiopia, the prevalence of diarrhea among children under the age of five remains high and is still a public health problem. The contributing factors to acute diarrheal illnesses were child, parental, and WASH factors. A continued focus on improving access to WASH facilities, along with enhancing maternal hygiene behavior will accelerate reductions in diarrheal disease burden in Ethiopia.
Topics: Humans; Ethiopia; Diarrhea; Child, Preschool; Infant; Prevalence; Observational Studies as Topic; Risk Factors
PubMed: 38903206
DOI: 10.3389/ijph.2024.1606399 -
ACS ES&T Water Jun 2024Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health....
Contaminated drinking water from widespread environmental pollutants such as perfluoroalkyl and polyfluoroalkyl substances (PFAS) poses a rising threat to public health. PFAS monitoring in groundwater is limited and fails to consider pesticides found to contain PFAS as a potential contamination source. Given previous findings on the disproportionate exposure of communities of Color to both pesticides and PFAS, we investigated disparities in PFAS-contaminated pesticide applications in California based on community-level sociodemographic characteristics. We utilized statewide pesticide application data from the California Department of Pesticide Regulation and recently reported concentrations of PFAS chemicals detected in eight pesticide products to calculate the areal density of PFAS applied within 1 km of individual community water systems' (CWSs) supply wells. Spatial regression analyses suggest that statewide, CWSs that serve a greater proportion of Latinx and non-Latinx People of Color residents experience a greater areal density of PFAS applied and greater likelihood of PFAS application near their public supply wells. These results highlight agroecosystems as potentially important sources of PFAS in drinking water and identify areas that may be at risk of PFAS contamination and warrant additional PFAS monitoring and remediation.
PubMed: 38903201
DOI: 10.1021/acsestwater.3c00845