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1.
Mar Environ Res ; 201: 106666, 2024 Aug 03.
Article in English | MEDLINE | ID: mdl-39133969

ABSTRACT

The present study aimed to investigate the effects of europium (Eu) exposure (10 µg/L), warming (a 4 °C increase), and their combination on Mytilus galloprovincialis. Biochemical and histopathological changes in adult mussels were evaluated after a 28-day exposure period. Additionally, biochemical and physiological alterations in sperm were measured following a 30-min exposure period. The overall responses to each treatment were assessed using the Integrated Biological Response index version 2 (IBRv2). In adult mussels, warming elevated metabolism and activated glutathione S-transferases (GSTs), leading to redox imbalance and cellular damage. Europium exposure alone slightly enhanced metabolism and GSTs activity, resulting in cellular damage and histopathological injuries in digestive tubules. The combined exposure to Eu and warming was the most detrimental treatment for adults, as indicated by the highest IBRv2 value. This treatment slightly increased metabolism and uniquely elevated the activity of antioxidant enzymes, as well as GSTs and carboxylesterases. Despite these responses, they were inadequate to prevent redox imbalance, cellular damage, and histopathological injuries in digestive tubules and gills. Regarding sperm, warming reduced reactive oxygen species (ROS) production but raised lipid peroxidation levels. Sperm exposed to this treatment also increased their oxygen consumption and exhibited reduced velocity. The IBRv2 indicated that Eu was the most harmful treatment for sperm, significantly increasing ROS production and notably decreasing sperm velocity. When combined with warming, Eu elevated superoxide anion (O2-) production, lowered sperm velocity, and increased oxygen consumption. This study underscores the importance of investigating the effects of rare earth elements and their interaction with climate change-related factors.

2.
Nutrients ; 16(13)2024 Jun 21.
Article in English | MEDLINE | ID: mdl-38999736

ABSTRACT

The etiology and mechanisms of autism and autism spectrum disorder (ASD) are not yet fully understood. There is currently no treatment for ASD for providing significant improvement in core symptoms. Recent studies suggest, however, that ASD is associated with gut dysbiosis, indicating that modulation of gut microbiota in children with ASD may thus reduce the manifestation of ASD symptoms. The aim of this pilot study (prospective randomized, double-blinded, placebo-controlled) was to evaluate efficacy of the biological response modifier Juvenil in modulating the microbiome of children with ASD and, in particular, whether Juvenil is able to alleviate the symptoms of ASD. In total, 20 children with ASD and 12 neurotypical children were included in our study. Supplementation of ASD children lasted for three months. To confirm Juvenil's impact on the gut microbiome, stool samples were collected from all children and the microbiome's composition was analyzed. This pilot study demonstrated that the gut microbiome of ASD children differed significantly from that of healthy controls and was converted by Juvenil supplementation toward a more neurotypical microbiome that positively modulated children's autism symptoms.


Subject(s)
Autism Spectrum Disorder , Dietary Supplements , Gastrointestinal Microbiome , Humans , Pilot Projects , Double-Blind Method , Male , Female , Autism Spectrum Disorder/microbiology , Child , Feces/microbiology , Child, Preschool , Prospective Studies , Autistic Disorder/microbiology , Dysbiosis/microbiology
3.
Pharmacol Rep ; 76(4): 823-837, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38888724

ABSTRACT

BACKGROUND: Traditional small-molecule chemotherapeutics usually do not distinguish tumors from healthy tissues. However, nanotechnology creates nanocarriers that selectively deliver drugs to their site of action. This work is the next step in the development of the quantum dot-ß-cyclodextrin-folic acid (QD-ß-CD-FA) platform for targeted and selected delivery of C-2028 unsymmetrical bisacridine in cancer therapy. METHODS: Herein, we report an initial biological evaluation (using flow cytometry and light microscopy) as well as cell migration analysis of QD-ß-CD(C-2028)-FA nanoconjugate and its components in the selected human lung and prostate cancer cells, as well as against their respective normal cells. RESULTS: C-2028 compound induced apoptosis, which was much stronger in cancer cells compared to normal cells. Conjugation of C-2028 with QDgreen increased cellular senescence, while the introduction of FA to the conjugate significantly decreased this process. C-2028 nanoencapsulation also reduced cell migration. Importantly, QDgreen and QDgreen-ß-CD-FA themselves did not induce any toxic responses in studied cells. CONCLUSIONS: In conclusion, the results demonstrate the high potential of a novel folic acid-targeted receptor quantum dot-ß-cyclodextrin carrier (QDgreen-ß-CD-FA) for drug delivery in cancer treatment. Nanoplatforms increased the amount of delivered compounds and demonstrated high suitability.


Subject(s)
Apoptosis , Drug Carriers , Folic Acid , Lung Neoplasms , Prostatic Neoplasms , Quantum Dots , beta-Cyclodextrins , Humans , Male , beta-Cyclodextrins/chemistry , Folic Acid/chemistry , Folic Acid/administration & dosage , Prostatic Neoplasms/drug therapy , Prostatic Neoplasms/pathology , Lung Neoplasms/drug therapy , Lung Neoplasms/pathology , Quantum Dots/chemistry , Apoptosis/drug effects , Drug Carriers/chemistry , Cell Movement/drug effects , Antineoplastic Agents/pharmacology , Antineoplastic Agents/administration & dosage , Acridines/pharmacology , Acridines/administration & dosage , Acridines/chemistry , Cell Line, Tumor , Drug Delivery Systems
4.
Waste Manag ; 186: 166-175, 2024 Sep 15.
Article in English | MEDLINE | ID: mdl-38905906

ABSTRACT

Tetracycline is an antibiotic with extensive veterinary use in the livestock industry. However, their widespread application poses risks to soil health as residue in livestock feces, and their removal is crucial for sustainable soil-ecosystem development. Physical and chemical approaches to extract tetracycline may have adverse effects on soil ecosystems, but no studies have thus far examined the potential for biological methods, such as collective degradation action of soil fauna. Thus, this study aimed to investigate the synergistic effects of lactic acid bacteria (LAB) and earthworms (Eisenia fetida) on biodegradation of tetracycline residues in sheep manure. We assessed earthworm biomass, tetracycline residue, and bacterial communities in both earthworm intestines and vermicompost. Earthworm biomass and tetracycline degradation efficiency increased significantly with LAB addition, with a degradation rate of up to 80.16%. This increase may be attributable to LAB acting as electron donors to spur tetracycline degradation. Additionally, we noted that tetracycline presence significantly influenced bacterial communities in earthworm intestines and vermicompost, elevating the abundance of potential pathogenic bacteria (e.g., Flavobacterium, Gammaproteobacteria, and Enterobacteriaceae). This finding suggests that heightened environmental stress from antibiotics could actually facilitate the growth of less prevalent bacteria, including potential pathogens. In conclusion, our study provides evidence supporting the effectiveness of LAB and earthworms in degrading tetracycline residues. In particular, LAB appears to mitigate stress from tetracycline exposure in earthworms, thus increasing their vermicomposting efficacy. Our work has important implications for soil management, with the potential to enhance pollution clean-up rates while minimizing negative side-effects to soil microbial communities.


Subject(s)
Biodegradation, Environmental , Lactobacillales , Livestock , Manure , Oligochaeta , Tetracycline , Oligochaeta/metabolism , Animals , Manure/microbiology , Lactobacillales/metabolism , Sheep , Soil Pollutants/metabolism , Soil Pollutants/analysis , Anti-Bacterial Agents , Soil Microbiology
5.
Pharm Biol ; 62(1): 367-393, 2024 Dec.
Article in English | MEDLINE | ID: mdl-38745507

ABSTRACT

CONTEXT: Rice bran arabinoxylan compound (RBAC) is a natural immunomodulator with anticancer properties. OBJECTIVE: This study critically evaluates the available evidence on the biological pathways of RBAC and its effects on cancer treatment. METHODS: This secondary analysis of a scoping review includes studies evaluating the mechanisms of RBAC on healthy or malignant cells, animal models, or humans for cancer prevention or treatment. Data from randomized controlled trials on survival and quality of life outcomes were subjectd to meta analysis. RESULTS: The evidence synthesis was based on 38 articles. RBAC exhibited antitumor properties by promoting apoptosis and restoring immune function in cancer patients to enhance inflammatory and cytotoxic responses to block tumorigenesis. RBAC works synergistically with chemotherapeutic agents by upregulating drug transport. In a clinical trial, combining RBAC with chemoembolization in treating liver cancer showed improved response, reduced recurrence rates, and prolonged survival. RBAC also augments the endogenous antioxidant system to prevent oxidative stress and protect against radiation side effects. In addition, RBAC has chemoprotective effects. Animals and humans have exhibited reduced toxicity and side effects from chemotherapy. Meta analysis indicates that RBAC treatment increases the survival odds by 4.02-times (95% CI: 1.67, 9.69) in the first year and 2.89-times (95% CI: 1.56, 5.35) in the second year. CONCLUSION: RBAC is a natural product with immense potential in cancer treatment. Additional research is needed to characterize, quantify, and standardize the active ingredients in RBAC responsible for the anticancer effects. More well-designed, large-scale clinical trials are required to substantiate the treatment efficacies further.


Subject(s)
Neoplasms , Oryza , Xylans , Xylans/pharmacology , Humans , Animals , Neoplasms/drug therapy , Biological Products/pharmacology , Antineoplastic Agents, Phytogenic/pharmacology , Antineoplastic Agents, Phytogenic/administration & dosage , Randomized Controlled Trials as Topic , Antineoplastic Agents/pharmacology
6.
J Funct Biomater ; 15(4)2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38667548

ABSTRACT

Zirconia ceramic implants are commercially available from a rapidly growing number of manufacturers. Macroscopic and microscopic surface design and characteristics are considered to be key determining factors in the success of the osseointegration process. It is, therefore, crucial to assess which surface modification promotes the most favorable biological response. The purpose of this study was to conduct a comparison of modern surface modifications that are featured in the most common commercially available zirconia ceramic implant systems. A review of the currently available literature on zirconia implant surface topography and the associated bio-physical factors was conducted, with a focus on the osseointegration of zirconia surfaces. After a review of the selected articles for this study, commercially available zirconia implant surfaces were all modified using subtractive protocols. Commercially available ceramic implant surfaces were modified or enhanced using sandblasting, acid etching, laser etching, or combinations of the aforementioned. From our literature review, laser-modified surfaces emerged as the ones with the highest surface roughness and bone-implant contact (BIC). It was also found that surface roughness could be controlled to achieve optimal roughness by modifying the laser output power during manufacturing. Furthermore, laser surface modification induced a very low amount of preload microcracks in the zirconia. Osteopontin (OPN), an early-late osteogenic differentiation marker, was significantly upregulated in laser-treated surfaces. Moreover, surface wettability was highest in laser-treated surfaces, indicating favorable hydrophilicity and thus promoting early bone forming, cell adhesion, and subsequent maturation. Sandblasting followed by laser modification and sandblasting followed by acid etching and post-milling heat treatment (SE-H) surfaces featured comparable results, with favorable biological responses around zirconia implants.

7.
World J Gastrointest Surg ; 16(3): 670-680, 2024 Mar 27.
Article in English | MEDLINE | ID: mdl-38577098

ABSTRACT

BACKGROUND: Although intracorporeal anastomosis (IA) for colon cancer requires longer operative time than extracorporeal anastomosis (EA), its short-term postoperative results, such as early recovery of bowel movement, have been reported to be equal or better. As IA requires opening the intestinal tract in the abdominal cavity under pneumoperitoneum, there are concerns about intraperitoneal bacterial infection and recurrence of peritoneal dissemination due to the spread of bacteria and tumor cells. However, intraperitoneal bacterial contamination and medium-term oncological outcomes have not been clarified. AIM: To clarify the effects of bacterial and tumor cell contamination of the intra-abdominal cavity in IA. METHODS: Of 127 patients who underwent laparoscopic colon resection for colon cancer from April 2015 to December 2020, 75 underwent EA (EA group), and 52 underwent IA (IA group). After propensity score matching, the primary endpoint was 3-year disease-free survival rates, and secondary endpoints were 3-year overall survival rates, type of recurrence, surgical site infection (SSI) incidence, number of days on antibiotics, and postoperative biological responses. RESULTS: Three-year disease-free survival rates did not significantly differ between the IA and EA groups (87.2% and 82.7%, respectively, P = 0.4473). The 3-year overall survival rates also did not significantly differ between the IA and EA groups (94.7% and 94.7%, respectively; P = 0.9891). There was no difference in the type of recurrence between the two groups. In addition, there were no significant differences in SSI incidence or the number of days on antibiotics; however, postoperative biological responses, such as the white blood cell count (10200 vs 8650/mm3, P = 0.0068), C-reactive protein (6.8 vs 4.5 mg/dL, P = 0.0011), and body temperature (37.7 vs 37.5 °C, P = 0.0079), were significantly higher in the IA group. CONCLUSION: IA is an anastomotic technique that should be widely performed because its risk of intraperitoneal bacterial contamination and medium-term oncological outcomes are comparable to those of EA.

8.
Cureus ; 16(1): e53188, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38425632

ABSTRACT

Background The effect of rice bran arabinoxylan compound (RBAC), a plant-based immunomodulator, on the quality of life (QoL) in cancer patients and underlying physiological pathways remains unclear. Trial design The RBAC-QoL study, a double-blind, randomised, controlled pilot feasibility study, aimed to determine RBAC's effects on QoL and the associated action mechanisms. Primary outcomes were the EORTC QLQ-C30 functional, symptom, and global QoL scores with inflammatory, nutritional, and cytokine parameters as secondary and exploratory outcomes. Methods Participants were adults diagnosed with solid organ tumours (≥ stage II) undergoing active treatment in several outpatient centres in New South Wales, Australia. Interventions were RBAC or matched placebo at 3g/day for 24 weeks allocated through stratified randomisation with participants, oncologists, and data collectors blinded. Data was collected from five study visits six weeks apart. The trial remained ongoing as of December 2023. An interim intention-to-treat analysis was performed using repeated measure ANOVA with pairwise comparisons where statistical significance was observed and adjusted with covariates. Results Global QoL scores from currently available data (n = 16; RBAC = 7, placebo = 9) were statistically different between groups (F1,8 = 8.6, p = 0.019, eta2[g] = 0.267). Pairwise comparisons found significant differences at Week 6 (p = 0.032, Cohen's d = 1.454) and marginally at Week 12 (p = 0.069, d = 1.427). Age-adjusted analysis showed a continuous upward trend in QoL improvement over time with RBAC, while the placebo group did not deviate from baseline QoL. Significant elevations of serum white blood cell count (Week 18) and total protein (Weeks 12 and 18) were detected in the RBAC group compared to placebo. The total protein levels correlated highly with white blood cell count (Pearson's r = 0.539, p < 0.001) and moderately with the global QoL scores (r = 0.338, p = 0.01). No intervention-related adverse events were reported in both groups.  Conclusions RBAC improves QoL beyond placebo during active cancer treatment, possibly through the immuno-nutritional pathway - these findings, though preliminary, are valuable for future research. Funding and registration: Daiwa Pharmaceutical Co., Ltd, Japan; BioMedica Nutraceuticals Pty Ltd., Australia. ANZCTR Reg No: ACTRN12619000562178p.

9.
Sci Total Environ ; 924: 171678, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38485016

ABSTRACT

The ubiquity of amino antioxidants (AAOs) in the environment has attracted increasing attention, given their potential toxicity. This investigation represents a pioneering effort, systematically scrutinizing the toxicological effects of four distinct AAOs across the developmental spectrum of zebrafish, encompassing embryonic, larvae, and adult stages. The results indicate that four types of AAO exhibit varying degrees of cell proliferation toxicity. Although environmentally relevant concentrations of AAOs exhibit a comparatively circumscribed impact on zebrafish embryo development, heightened concentrations (300 µg/L) of N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine (6PPD) and N-isopropyl-N'-phenyl-p-phenylenediamine (IPPD) distinctly evoke developmental toxicity. Behavioral analysis results indicate that at concentrations of 20 and 300 µg/L, the majority of AAOs significantly reduced the swimming speed and activity of larvae. Moreover, each AAO triggers the generation of reactive oxygen species (ROS) in larvae, instigating diverse levels of oxidative stress. The study delineates parallel toxicological patterns in zebrafish exposed to 300 µg/L of 6PPD and IPPD, thereby establishing a comparable toxicity profile. The comprehensive toxicity effects among the four AAOs is as follows: IPPD >6PPD > N-Phenyl-1-naphthylamine (PANA) > diphenylamine (DPA). These findings not only enrich our comprehension of the potential hazards associated with AAOs but also provide data support for structure-based toxicity prediction models.


Subject(s)
Water Pollutants, Chemical , Zebrafish , Animals , Zebrafish/physiology , Antioxidants/metabolism , Phenylenediamines/toxicity , Oxidative Stress , Larva , Embryo, Nonmammalian , Water Pollutants, Chemical/metabolism
10.
Vet Res Commun ; 48(3): 1573-1593, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38409399

ABSTRACT

The safety and effectiveness of oxytetracycline can potentially manage bacterial infections in fish. This, in turn, might reduce the concerns related to its use in aquaculture and human consumption, such as toxicity, antimicrobial resistance, and other associated risks. The primary objective of this study was to assess how adding oxytetracycline dihydrate to the diet affects its effectiveness, safety, and the presence of residues in T. putitora. T. putitora fingerlings, subjected to experimental infection with Aeromonas hydrophila at a concentration of 108 CFU mL- 1, received an oral administration of oxytetracycline dihydrate. The oxytetracycline dihydrate was added to the feed (corresponding to 2% of the fish body weight) at concentrations of 44.1, 88.2, 132.3 and 176.4 mg Kg- 1 fish body weight per day. This treatment was carried out for 10 consecutive days. The biochemical and physiological responses of T. putitora and efficacy of oxytetracycline dihydrate were determined through estimation of microbial load (CFU mL- 1), haematogram, serum biomarkers, behavioral characteristics, non-specific immunity and residue depletion. Experimentally infected fish showed disease progression and induced histopathological conditions with highest microbial load (CFU mL- 1) in the muscle of both control and treated fish. The fish haematogram showed increased leucocyte and haemoglobin content, influenced by dietary oxytetracycline dihydrate. The fish demonstrated adaptive physiological response to oxytetracycline dihydrate at 44.1 to 88.2 mg and resulted in increased albumin and globulin content. The serum-enzyme assay showed significant increase in aspartate aminotransferase (AST), alanine aminotransferase (ALT) and plasma alkaline phosphatase (ALP) activities in the test fish (< 0.05). Oxytetracycline dihydrate at 88.2 to 132.3 mg Kg- 1 fish body weight per day recorded higher feed intake (75%), significant survivability (66-68%) and histopathological recovery. The suppressed immune response was manifested with decreased respiratory burst and lysozyme activity. The palatability, treatment of bacterial infection, histopathological changes and survivability by fingerlings of golden mahseer determined the safety and optimized the therapeutic potential of the oxytetracycline dihydrate at 88.2 mg Kg- 1 fish body weight per day for 10 days to contain the infection by A. hydrophila. A withdrawal period of 8-d was recommended as oxytetracycline dihydrate concentration depleted below the legal maximum residue limit (MRL 2.0 mg g- 1) in the edible muscle of the golden mahseer reared at an average water temperature of 20 °C. This is considered safe for human consumption.


Subject(s)
Animal Feed , Anti-Bacterial Agents , Cyprinidae , Dietary Supplements , Fish Diseases , Oxytetracycline , Animals , Oxytetracycline/pharmacology , Oxytetracycline/administration & dosage , Animal Feed/analysis , Fish Diseases/drug therapy , Fish Diseases/microbiology , Dietary Supplements/analysis , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/administration & dosage , Cyprinidae/physiology , Diet/veterinary , Drug Residues/analysis , Aeromonas hydrophila/drug effects , Aeromonas hydrophila/physiology , Dose-Response Relationship, Drug , Gram-Negative Bacterial Infections/veterinary , Gram-Negative Bacterial Infections/drug therapy
11.
Chemosphere ; 352: 141268, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38246499

ABSTRACT

Swimming consistency and respiration of fish are recognized as the non-invasive stress biomarkers. Their alterations could directly indicate the presence of pollutants in the water ecosystem. Since these biomarkers are a routine process for fish, it is difficult to monitor their activity manually. For this reason, experts employ engineering technologies to create sensors that can monitor the regular activities of fish. Knowing the importance of these non-invasive stress biomarkers, we developed online biological behavior monitoring system-OBBMS and online biological respiratory response monitoring system-OBRRMS to monitor real-time swimming consistency and respiratory response of fish, respectively. We continuously monitored the swimming consistency and respiration (OCR, CER and RQ) of zebrafish (control and atrazine-treatments) for 7 days using our homemade real-time biological response monitoring systems. Furthermore, we analyzed oxidative stress indicators (SOD, CAT and POD) within the vital tissues (gills, brain and muscle) of zebrafish during stipulated sampling periods. The differences in the swimming consistency and respiratory rate of zebrafish between the control and atrazine treatments could be precisely differentiated on the real-time datasets of OBBMS and OBRRMS. The zebrafish exposed to atrazine toxin showed a concentration-dependent effect (hypoactivity). The OCR and CER were increased in the atrazine treated zebrafish. Both Treatment I and II received a negative response for RQ. Atrazine toxicity let to a rise in the levels of SOD, CAT and POD in the vital tissues of zebrafish. The continuous acquisition of fish signals is achieved which is one of the main merits of our OBBMS and OBRRMS. Additionally, no special data processing was done, the real-time data sets were directly used on statistical tools and the differences between the factors (groups, photoperiods, exposure periods and their interactions) were identified precisely. Hence, our OBBMS and OBRRMS could be a promising tool for biological response-based real-time water quality monitoring studies.


Subject(s)
Atrazine , Perciformes , Water Pollutants, Chemical , Animals , Antioxidants , Zebrafish/physiology , Swimming , Atrazine/toxicity , Water Quality , Ecosystem , Respiration , Superoxide Dismutase , Biomarkers , Water Pollutants, Chemical/toxicity
12.
J Clin Lab Anal ; 38(1-2): e24994, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38069592

ABSTRACT

BACKGROUND: Platelet concentrate (PC) transfusions are crucial in prevention and treatment of bleeding in infection, surgery, leukemia, and thrombocytopenia patients. Although the technology for platelet preparation and storage has evolved over the decades, there are still challenges in the demand for platelets in blood banks because the platelet shelf life is limited to 5 days due to bacterial contamination and platelet storage lesions (PSLs) at 20-24°C under constant horizontal agitation. In addition, the relations between some adverse effects of platelet transfusions and PSLs have also been considered. Therefore, understanding the mechanisms of PSLs is conducive to obtaining high quality platelets and facilitating safe and effective platelet transfusions. OBJECTIVE: This review summarizes developments in mechanistic research of PSLs and their relationship with clinical practice, providing insights for future research. METHODS: Authors conducted a search on PubMed and Web of Science using the professional terms "PSL" and "platelet transfusion." The obtained literature was then roughly categorized based on their research content. Similar studies were grouped into the same sections, and further searches were conducted based on the keywords of each section. RESULTS: Different studies have explored PSLs from various perspectives, including changes in platelet morphology, surface molecules, biological response modifiers (BMRs), metabolism, and proteins and RNA, in an attempt to monitor PSLs and identify intervention targets that could alleviate PSLs. Moreover, novel platelet storage conditions, including platelet additive solutions (PAS) and reconsidered cold storage methods, are explored. There are two approaches to obtaining high-quality platelets. One approach simulates the in vivo environment to maintain platelet activity, while the other keeps platelets at a low activity level in vitro under low temperatures. CONCLUSION: Understanding PSLs helps us identify good intervention targets and assess the therapeutic effects of different PSLs stages for different patients.


Subject(s)
Blood Platelets , Thrombocytopenia , Humans , Blood Platelets/metabolism , Platelet Transfusion/methods , Hemorrhage , Blood Banks , Blood Preservation/methods
13.
Ann Biomed Eng ; 52(1): 89-102, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37115366

ABSTRACT

High-voltage pulsed electric fields (HV-PEF) delivered with invasive needle electrodes for electroporation applications is known to induce off-target blood-brain barrier (BBB) disruption. In this study, we sought to determine the feasibility of minimally invasive PEF application to produce BBB disruption in rat brain and identify the putative mechanisms mediating the effect. We observed dose-dependent presence of Evans Blue (EB) dye in rat brain when PEF were delivered with a skull mounted electrode used for neurostimulation application. Maximum region of dye uptake was observed while using 1500 V, 100 pulses, 100 µs and 10 Hz. Results of computational models suggested that the region of BBB disruption was occurring at thresholds of 63 V/cm or higher; well below intensity levels for electroporation. In vitro experiments recapitulating this effect with human umbilical vein endothelial cells (HUVEC) demonstrated cellular alterations that underlie BBB manifests at low-voltage high-pulse conditions without affecting cell viability or proliferation. Morphological changes in HUVECs due to PEF were accompanied by disruption of actin cytoskeleton, loss of tight junction protein-ZO-1 and VE-Cadherin at cell junctions and partial translocation into the cytoplasm. Uptake of propidium iodide (PI) in PEF treated conditions is less than 1% and 2.5% of total number of cells in high voltage (HV) and low-voltage (LV) groups, respectively, implying that BBB disruption to be independent of electroporation under these conditions. 3-D microfabricated blood vessel permeability was found to increase significantly following PEF treatment and confirmed with correlative cytoskeletal changes and loss of tight junction proteins. Finally, we show that the rat brain model can be scaled to human brains with a similar effect on BBB disruption characterized by electric field strength (EFS) threshold and using a combination of two bilateral HD electrode configurations.


Subject(s)
Blood-Brain Barrier , Endothelial Cells , Humans , Rats , Animals , Blood-Brain Barrier/metabolism , Endothelial Cells/physiology , Biological Transport , Brain , Gap Junctions/metabolism
14.
J Agric Food Chem ; 71(31): 11902-11920, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37490609

ABSTRACT

Heat stress (HS) negatively influences cows' welfare and productivity. Therefore, a better understanding of the physiological and molecular mechanisms of HS responses from multiple parities is paramount for the development of effective management and breeding strategies. In comparison with first-parity cows in the spring (Spring-1), first-parity cows in the summer (Summer-1) had a significantly higher rectal temperature (RT), respiration rate (RR), drooling score (DS), and daily activity (DA), while lower (P < 0.05) daily rumination (DR), seven-day average milk yield (7AMY), milk yield on sampling day (MY_S), milk yield on test day (MY_T), and lactose percentage (LP) were observed. When comparing the spring (Spring-2) and summer (Summer-2) of the second-parity cows, significant differences were also found in RT, RR, DS, DA, and DR (P < 0.05), corresponding to similar trends with the first parity while having smaller changes. Moreover, significantly negative impacts on performance traits were only observed on fat percentage (FP) and LP. These results showed that there were different biological responses between first- and second-parity Holstein cows. Further, 18 and 17 metabolites were involved in the seasonal response of first- and second-parity cows, respectively. Nine differential metabolites were shared between the two parities, and pathway analyses suggested that cows had an inhibited tricarboxylic acid cycle, increased utilization of lipolysis, and a dysregulated gut microbiome during the summer. The metabolites identified exclusively for each parity highlighted the differences in microbial response and host amino acid metabolism between two parities in response to HS. Moreover, glucose, ethanol, and citrate were identified as potential biomarkers for distinguishing individuals between Spring-1 and Summer-1. Ethanol and acetone were better predictors for distinguishing individuals between Spring-2 and Summer-2. Taken together, the present study demonstrated the impact of naturally induced HS on physiological parameters, production traits, and the blood metabolome of Holstein cows. There are different biological responses and regulation mechanisms between first- and second-parity Holstein cows.


Subject(s)
Lactation , Milk , Animals , Cattle , Female , Pregnancy , Heat-Shock Response , Lactation/physiology , Milk/chemistry , Parity , Seasons
15.
Environ Pollut ; 335: 122261, 2023 Oct 15.
Article in English | MEDLINE | ID: mdl-37499971

ABSTRACT

Perfluorooctanoic acid (PFOA) is a type of toxic per- and poly-fluoroalkyl substance (PFAS) commonly found in groundwater due to its use in firefighting and industrial applications. The main purpose of this study was to investigate the influence of PFOA shock on the biological performance of a hydrogen-driven bioreactor for nitrate and arsenate removal. Four hydrogen-driven removal reactors (HdBRs) used for the simultaneous removal of nitrate and arsenal were operated with concentrations of either 0, 1, 5, and 10 mg/L of PFOA to induce shock on the systems and examine the corresponding bacterial response. Our results showed that PFOA shock inhibited and decreased the maximum hydrogen-driven arsenate removal rate. Principal Component Analysis (PCA) confirmed that this performance decrease occurred due to a bacterial strike triggered by PFOA shock. PFOA toxicity also led to protein secretion and sludge density decreases. Bacterial analyses showed shifts in the community population due to PFOA shock. The dominant bacteria phylum Proteobacteria became more abundant, from 41.24% originally to 48.29% after exposure to 10 mg/L of PFOA. Other phyla, such as Euryarchaeota and Bacteroidetes, were more tolerant to PFOA shock. Although some of the predominant species within the sludge of each HdBR exhibited a decline, other species with similar functions persisted and assumed the functional responsibilities previously held by the dominant species.


Subject(s)
Fluorocarbons , Nitrates , Nitrates/metabolism , Sewage , Arsenates/metabolism , Fluorocarbons/toxicity , Fluorocarbons/metabolism , Caprylates/metabolism , Bacteria/metabolism
16.
Biology (Basel) ; 12(5)2023 Apr 27.
Article in English | MEDLINE | ID: mdl-37237473

ABSTRACT

The continental shelves of the Weddell Sea and the Antarctic Peninsula vicinity host abundant macrobenthic communities, and the persistence of which is facing serious global change threats. The current relationship among pelagic energy production, its distribution over the shelf, and macrobenthic consumption is a "clockwork" mechanism that has evolved over thousands of years. Together with biological processes such as production, consumption, reproduction, and competence, it also involves ice (e.g., sea ice, ice shelves, and icebergs), wind, and water currents, among the most important physical controls. This bio-physical machinery undergoes environmental changes that most likely will compromise the persistence of the valuable biodiversity pool that Antarctic macrobenthic communities host. Scientific evidence shows that ongoing environmental change leads to primary production increases and also suggests that, in contrast, macrobenthic biomass and the organic carbon concentration in the sediment may decrease. Warming and acidification may affect the existence of the current Weddell Sea and Antarctic Peninsula shelf macrobenthic communities earlier than other global change agents. Species with the ability to cope with warmer water may have a greater chance of persisting together with allochthonous colonizers. The Antarctic macrobenthos biodiversity pool is a valuable ecosystem service that is under serious threat, and establishing marine protected areas may not be sufficient to preserve it.

17.
Food Sci Nutr ; 11(4): 1634-1656, 2023 Apr.
Article in English | MEDLINE | ID: mdl-37051359

ABSTRACT

Vitamin K1 (VitK1) and Vitamin K2 (VitK2), two important naturally occurring micronutrients in the VitK family, found, respectively, in green leafy plants and algae (VitK1) and animal and fermented foods (VitK2). The present review explores the multiple biological functions of VitK2 from recently published in vitro and in vivo studies, including promotion of osteogenesis, prevention of calcification, relief of menopausal symptoms, enhancement of mitochondrial energy release, hepato- and neuro-protective effects, and possible use in treatment of coronavirus disease. The mechanisms of action associated with these biological effects are also explored. Overall, the findings presented here suggest that VitK, especially VitK2, is an important nutrient family for the normal functioning of human health. It acts on almost all major body systems and directly or indirectly participates in and regulates hundreds of physiological or pathological processes. However, as biological and clinical data are still inconsistent and conflicting, more in-depth investigations are warranted to elucidate its potential as a therapeutic strategy to prevent and treat a range of disease conditions.

18.
J Clin Biochem Nutr ; 72(2): 107-116, 2023 Mar.
Article in English | MEDLINE | ID: mdl-36936873

ABSTRACT

The impact of radiation-induced hydrogen peroxide (H2O2) on the biological effects of X-rays and carbon-ion beams was investigated using a selenium-deficient (SeD) mouse model. Selenium is the active center of glutathione peroxidase (GSH-Px), and SeD mice lack the ability to degrade H2O2. Male and female SeD mice were prepared by feeding a torula yeast-based SeD diet and ultrapure water. Thirty-day survival rates after whole-body irradiation, radiation-induced leg contracture, and MRI-based redox imaging of the brain were assessed and compared between SeD and normal mice. Thirty-day lethality after whole-body 5.6 Gy irradiation with X-rays or carbon-ion beams was higher in the SeD mice than in the normal mice, while SeD did not give the notable difference between X-rays and carbon-ion beams. SeD also did not affect the maximum leg contracture level after irradiation with carbon-ion beams, but delayed the leg contraction rate. In addition, no marked effects of SeD were observed on variations in the redox status of the brain after irradiation. Collectively, the present results indicate that SeD slightly altered the biological effects of X-rays and/or carbon-ion beams. GSH-Px processes endogenous H2O2 generated through mitochondrial respiration, but does not have the capacity to degrade H2O2 produced by irradiation.

19.
Ann Pharmacother ; 57(9): 1094-1110, 2023 09.
Article in English | MEDLINE | ID: mdl-36600576

ABSTRACT

OBJECTIVE: To describe and review the published evidence on use of multiple biologics within specialty pharmacy practice. DATA SOURCES: A search of PubMed and Embase was conducted from October 2021 through September 2022. Keywords included biologics for immune-mediated conditions along with the terms "dual," "add-on," and "combination." STUDY SELECTION AND DATA EXTRACTION: All human studies in the English language were considered. Published abstracts, case reports, case series, randomized controlled trials, systematic reviews, and meta-analyses were included. DATA SYNTHESIS: Although evidence is limited, there are published meta-analyses of combined biologic use within gastroenterology and rheumatology. There are also numerous case reports within dermatology. Clinical trials of dual biologics for severe rheumatologic conditions and inflammatory bowel disease are in progress. Existing evidence for use in pulmonology and allergy suggest dual biologic therapy can be safe and effective, but data are limited. Literature describing use of monoclonal antibodies for other overlapping conditions is lacking. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This article reviews the evidence describing combination biologic use and outlines remaining knowledge gaps. It also describes the essential role that specialty pharmacists play in managing therapeutic mAbs. CONCLUSIONS: High-quality evidence describing combination biologic use is limited and long-term safety data are lacking. Pharmacists should utilize their specialized training to assess appropriateness of therapy, provide patient counseling and monitor for safety and efficacy.


Subject(s)
Biological Products , Pharmaceutical Services , Pharmacy , Humans , Antibodies, Monoclonal/therapeutic use , Biological Products/therapeutic use
20.
Water Res ; 231: 119661, 2023 Mar 01.
Article in English | MEDLINE | ID: mdl-36716568

ABSTRACT

Climate change is projected to threaten ecological communities through changes in temperature, rainfall, runoff patterns, and mediated changes in other environmental variables. Their combined effects are difficult to comprehend without the mathematical machinery of causal modelling. Using piecewise structural equation modelling, we aim to predict the responses of aquatic macroinvertebrate total abundance and richness to disturbances generated by climate change. Our approach involves integrating an existing hydroclimate-salinity model for the Murray-Darling Basin, Australia, into our recently developed statistical models for macroinvertebrates using long-term monitoring data on macroinvertebrates, water quality, climate, and hydrology, spanning 2,300 km of the Murray River. Our exercise demonstrates the potential of causal modelling for integrating data and models from different sources. As such, optimal use of valuable existing data and merits of previously developed models in the field can be made for exploring the effects of future climate change and management interventions.


Subject(s)
Climate Change , Models, Theoretical , Models, Statistical , Water Quality , Australia , Rivers/chemistry , Environmental Monitoring , Ecosystem
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