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International Journal of Molecular... Jun 2024Ruthenium chloride (RuCl) is widely utilized for synthesis and catalysis of numerous compounds in academia and industry and is utilized as a key molecule in a variety of...
Ruthenium chloride (RuCl) is widely utilized for synthesis and catalysis of numerous compounds in academia and industry and is utilized as a key molecule in a variety of compounds with medical applications. Interestingly, RuCl has been demonstrated to modulate human plasmatic coagulation and serves as a constituent of a compounded inorganic antivenom that neutralizes the coagulopathic effects of snake venom in vitro and in vivo. Using thrombelastography, this investigation sought to determine if RuCl inhibition of the fibrinogenolytic effects of venom could be modulated by vehicle composition in human plasma. Venom was exposed to RuCl in 0.9% NaCl, phosphate-buffered saline (PBS), or 0.9% NaCl containing 1% dimethyl sulfoxide (DMSO). RuCl inhibited venom-mediated delay in the onset of thrombus formation, decreased clot growth velocity, and decreased clot strength. PBS and DMSO enhanced the effects of RuCl. It is concluded that while a Ru-based cation is responsible for significant inhibition of venom activity, a combination of Ru-based ions containing phosphate and DMSO enhances RuCl-mediated venom inhibition. Additional investigation is indicated to determine what specific Ru-containing molecules cause venom inhibition and what other combinations of inorganic/organic compounds may enhance the antivenom effects of RuCl.
Topics: Humans; Dimethyl Sulfoxide; Antivenins; Crotalid Venoms; Animals; Blood Coagulation; Crotalus; Ruthenium Compounds; Sodium Chloride; Thrombelastography; Venomous Snakes
PubMed: 38928132
DOI: 10.3390/ijms25126426 -
International Journal of Molecular... Jun 2024Eastern Diamondback Rattlesnake () envenomation is a medical emergency encountered in the Southeastern United States. The venom contains a snake venom thrombin-like...
Eastern Diamondback Rattlesnake () envenomation is a medical emergency encountered in the Southeastern United States. The venom contains a snake venom thrombin-like enzyme (SVTLE) that is defibrinogenating, causing coagulopathy without effects on platelets in humans. This investigation utilized thrombelastographic methods to document this coagulopathy kinetically on the molecular level in a rabbit model of envenomation via the analyses of whole blood samples without and with platelet inhibition. Subsequently, the administration of a novel ruthenium compound containing site-directed antivenom abrogated the coagulopathic effects of envenomation in whole blood without platelet inhibition and significantly diminished loss of coagulation in platelet-inhibited samples. This investigation provides coagulation kinetic insights into the molecular interactions and results of SVTLE on fibrinogen-dependent coagulation and confirmation of the efficacy of a ruthenium antivenom. These results serve as a rationale to investigate the coagulopathic effects of other venoms with this model and assess the efficacy of this site-directed antivenom.
Topics: Animals; Rabbits; Antivenins; Crotalus; Crotalid Venoms; Blood Coagulation; Thrombelastography; Ruthenium; Snake Bites; Male; Venomous Snakes
PubMed: 38928044
DOI: 10.3390/ijms25126334 -
Genes Jun 2024Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated...
Galectins are innate immune system regulators associated with disease progression in cancer. This paper aims to investigate the correlation between mutated cancer-critical genes and galectin levels in breast cancer patients to determine whether galectins and genetic profiles can be used as biomarkers for disease and potential therapy targets. Prisma Health Cancer Institute's Biorepository provided seventy-one breast cancer samples, including all four stages spanning the major molecular subtypes and histologies. Hotspot mutation statuses of cancer-critical genes were determined using multiplex PCR in tumor samples from the same patients by Precision Genetics and the University of South Carolina Functional Genomics Core Facility. The galectin-1, -3, and -9 levels in patients' sera were analyzed using Enzyme-linked Immunosorbent Assay (ELISA). An analysis was performed using JMP software to compare mean and median serum galectin levels between samples with and without specific cancer-critical genes, including pooled -test, Wilcoxon Rank Sum Test, ANOVA, and Steel Dwass Test (α=0.05). Our analysis indicates that mutations correlate with elevated serum levels of galectin-9 in patients with breast cancer. In patients with Luminal A subtype, mutation correlates with lower serum galectin-1 and -9 levels and mutations correlate with higher serum galectin-3 levels. Patients with invasive ductal carcinoma had significantly higher serum galectin-3 levels than patients with ductal carcinoma in situ. Patients with both and mutations exhibit elevated serum galectin-3 levels, while patients with one or neither mutation show no significant difference in serum galectin-3 levels. In addition, metastatic breast cancer samples were more likely to have a or mutation compared to primary breast cancer samples. The relationship between genetic mutations and galectin levels has the potential to identify appropriate candidates for combined therapy, targeting genetic mutations and galectins. Further understanding of the effect of genetic mutations and galectin levels on cancer progression and metastasis could aid in the search for biomarkers for breast cancer diagnosis, disease progression, and prognosis.
Topics: Humans; Breast Neoplasms; Female; Galectins; Mutation; Biomarkers, Tumor; Galectin 1; Middle Aged; Galectin 3; Adult; Blood Proteins
PubMed: 38927753
DOI: 10.3390/genes15060818 -
BMC Public Health Jun 2024To analyze the vulnerability factors of snakebite patients in China.
OBJECTIVE
To analyze the vulnerability factors of snakebite patients in China.
METHODS
Multi-stage random sampling was used as the main sampling method and snowball sampling as the auxiliary sampling method. The knowledge, attitude and behavior of snakebite among Chinese residents were investigated. Non-parametric test was used to compare the percentage differences in residents' knowledge, attitude and behavior of snakebite, and generalized linear regression analysis was used to analyze the influencing factors, and the vulnerability factors of snakebite patients were comprehensively analyzed.
RESULTS
A total of 6338 subjects were included in this study, of which 68.4% were males, and 58.6% were farmers, workers and service personnel. The median total score of knowledge, attitude, and behavior was 26 (22,36). The patients who were improperly treated after injury were ligation proximal to the affected area (23.43%), squeezing (21.82%), and oral and suction wounds (8.74%). Did not go to hospital due to poverty (1351 cases) and did not receive antivenom (2068 cases). There were 21.32% and 32.63%, respectively. Among 4270 patients injected with antivenom 30.7% were vaccinated within 2 h. Among the patients who went to the hospital for treatment (4987), 75.0% arrived at the hospital within 6 h; Among the 4,761 patients who made emergency calls, 37.4% were treated within 0.5 h.
CONCLUSIONS
Snakebite patients in China have weak knowledge about snakebite, low awareness of medical treatment, lack of correct prevention and emergency treatment measures, dependence on folk remedies, poor housing and so on. In addition, there are low availability of antivenoms and unreasonable distribution of medical resources in some areas of China. Multisectoral and multidisciplinary cooperation should be developed to prevent and control snakebites in order to reduce the burden caused by snakebites.
Topics: Snake Bites; Humans; China; Male; Female; Adult; Health Knowledge, Attitudes, Practice; Middle Aged; Young Adult; Adolescent; Antivenins; Risk Factors; Surveys and Questionnaires; Aged
PubMed: 38926898
DOI: 10.1186/s12889-024-19169-3 -
Veterinary Immunology and... Jun 2024Controlling pathogenic infections while reducing antibiotic usage is an important challenge during poultry production. In addition to vaccination strategies, several...
Controlling pathogenic infections while reducing antibiotic usage is an important challenge during poultry production. In addition to vaccination strategies, several solutions to enhance the immune response against pathogens are evaluated. In this study, we aim to determine the effects of the glycerides of lauric acid (GLA) supplementation in chickens' diets on humoral and cellular immune response pathogenic infections, using an in vivo model of infectious bronchitis virus (IBV). One-day-old Ross 308 broilers were vaccinated with live attenuated IBV and fed diets supplemented with or without GLA at 3 kg/ton. The levels of early (day 7) specific anti-IBV in sera were significantly increased in broilers fed GLA, compared to the control groups (P<0.05), showing a stronger primary humoral response. The secretion levels of main cytokines remained similar in spleens of all the experimental groups. However, the splenocytes from broilers fed GLA showed higher activation and effector abilities when measured by IFN-γ ELISpot in presence of N-261-280 IBV peptide or Concanavalin A (Con A), a pan T lymphocytes mitogen. In response to N-261-280 peptide, GLA group showed a 2-fold increase of spot numbers (P < 0.05) and 3-fold increase of spot surfaces (P < 0.01) compared to the control groups. Similarly, Con A stimulation showed a 2-fold increases in spot surfaces and numbers in the GLA supplemented group compared to the control group (P < 0.01). In summary, GLA supplementation in chicken feed enhances the primary humoral immune response and strengthen the T lymphocytes mediated cellular immune response. These findings demonstrate how GLA can improve chicken resilience against pathogenic challenges by enhancing their immune responses.
PubMed: 38924873
DOI: 10.1016/j.vetimm.2024.110802 -
Emerging Microbes & Infections Jun 2024The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was as high as 13%....
The proportion of human isolates with reduced neuraminidase inhibitors (NAIs) susceptibility in highly pathogenic avian influenza (HPAI) H7N9 virus was as high as 13%. These drug-resistant strains showed good replication capacity without serious loss of fitness. At the presence of oseltamivir, R229I substitution were found in HA1 region of the HPAI H7N9 virus before NA R292 K appeared. HPAI H7N9 or H7N9/PR8 recombinant viruses were developed to study whether HA R229I could increase the fitness of the H7N9 virus bearing NA 292 K. Replication efficiency was assessed in MDCK or A549 cells. Neuraminidase enzyme activity and receptor-binding ability were analyzed. The pathogenicity in C57 mice was evaluated. Antigenicity analysis was conducted through a two-way HI test, in which the antiserum was obtained from immunized ferrets. Transcriptomic analysis of MDCK infected with HPAI H7N9 24hpi was done. It turned out that HA R229I substitution from oseltamivir induction in HA1 region increased 1)replication ability in MDCK(< 0.05) and A549(< 0.05), 2)neuraminidase enzyme activity, 3)binding ability to both α2,3 and α2,6 receptor, 4)pathogenicity to mice(more weight loss; shorter mean survival day; viral titer in respiratory tract, < 0.05; Pathological changes in pneumonia), 5) transcriptome response of MDCK, of the H7N9 virus bearing NA 292 K. Besides, HA R229I substitution changed the antigenicity of H7N9/PR8 virus (>4-fold difference of HI titer). It indicated that through the fine-tuning of the HA-NA balance, R229I increased the fitness and change the antigenicity of a H7N9 virus bearing NA 292 K. Public health attention of this mechanism needs to be drawn.
PubMed: 38922326
DOI: 10.1080/22221751.2024.2373314 -
ImmunoHorizons Jun 2024The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the...
The underlying contribution of immune complexes in modulating adaptive immunity in mucosal tissues remains poorly understood. In this report, we examined, in mice, the proinflammatory response elicited by intranasal delivery of the biothreat agent ricin toxin (RT) in association with two toxin-neutralizing mAbs, SylH3 and PB10. We previously demonstrated that ricin-immune complexes (RICs) induce the rapid onset of high-titer toxin-neutralizing Abs that persist for months. We now demonstrate that such responses are dependent on CD4+ T cell help, because treatment of mice with an anti-CD4 mAb abrogated the onset of RT-specific Abs following intranasal RICs exposure. To define the inflammatory environment associated with RIC exposure, we collected bronchoalveolar lavage fluid (BALF) and sera from mice 6, 12, and 18 h after they had received RT or RICs by the intranasal route. A 32-plex cytometric bead array revealed an inflammatory profile elicited by RT that was dominated by IL-6 (>1500-fold increase in BALF) and secondarily by KC (CXCL1), G-CSF, GM-CSF, and MCP-1. RICs induced inflammatory profiles in both BALF and serum response that were similar to RT, albeit at markedly reduced levels. These results demonstrate that RICs retain the capacity to induce local and systemic inflammatory cytokines/chemokines that, in turn, may influence Ag sampling and presentation in the lung mucosa and draining lymph nodes. A better understanding of the fate of immune complexes following intranasal delivery has implications for the development of mucosal vaccines for biothreats and emerging infectious diseases.
Topics: Animals; Administration, Intranasal; Ricin; Mice; Bronchoalveolar Lavage Fluid; Female; Antigen-Antibody Complex; Antibodies, Neutralizing; Immunization; Inflammation; Antibodies, Monoclonal; Cytokines; CD4-Positive T-Lymphocytes; Mice, Inbred BALB C; Mice, Inbred C57BL
PubMed: 38922287
DOI: 10.4049/immunohorizons.2400007 -
Toxins May 2024The genus encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in... (Review)
Review
The genus encompasses most species of medically significant venomous snakes of Europe, with Italy harbouring four of them. Envenomation by European vipers can result in severe consequences, but underreporting and the absence of standardised clinical protocols hinder effective snakebite management. This study provides an updated, detailed set of guidelines for the management and treatment of snakebite tailored for Italian clinicians. It includes taxonomic keys for snake identification, insights into viper venom composition, and recommendations for clinical management. Emphasis is placed on quick and reliable identification of medically relevant snake species, along with appropriate first aid measures. Criteria for antivenom administration are outlined, as well as indications on managing potential side effects. While the protocol is specific to Italy, its methodology can potentially be adapted for other European countries, depending on local resources. The promotion of comprehensive data collection and collaboration among Poison Control Centres is advocated to optimise envenomation management protocols and improve the reporting of epidemiological data concerning snakebite at the country level.
Topics: Snake Bites; Italy; Viperidae; Animals; Antivenins; Humans; Viper Venoms; Vipera
PubMed: 38922149
DOI: 10.3390/toxins16060255 -
Toxins May 2024This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in...
Retrospective Evaluation of Clinical and Clinicopathologic Findings, Case Management, and Outcome for Dogs and Cats Exposed to (Eastern Coral Snake): 92 Cases (2021-2022).
This retrospective, observational study describes the clinical findings, case management trends, and outcomes of 83 dogs and nine cats exposed to eastern coral snakes in a university teaching hospital setting. The medical records of dogs and cats that received antivenom following coral snake exposure were reviewed. Data collected included signalment, time to antivenom administration, physical and laboratory characteristics at presentation, clinical course during hospitalization, length of hospitalization, and survival to discharge. The mean time from presentation to coral snake antivenom administration was 2.26 ± 1.46 h. Excluding cases where the owner declined in-hospital care, the mean hospitalization time for dogs and cats was 50.8 h and 34 h, respectively. The mean number of antivenom vials was 1.29 (1-4). Gastrointestinal signs (vomiting and ptyalism) occurred in 42.2% (35/83) of dogs and 33.3% (3/9) of cats. Peripheral neurologic system deficits (ataxia, paresis to plegia, absent reflexes, and hypoventilation) were noted in 19.6% (18/92) of dogs and cats. Hemolysis was also common in 37.9% (25/66) of dogs but was not observed in cats. Mechanical ventilation (MV) was indicated in 12% (10/83) of dogs but no cats. Acute kidney injury (AKI), while rare, was a common cause of euthanasia at 20% (2/5) and was the most common complication during MV at 44.4% (4/9). Pigmenturia/hemolysis occurred in 88.9% (8/9) of MV cases and in all cases with AKI. Despite delays in antivenom administration by several hours, dogs and cats with coral snake exposure have low mortality rates (6% of dogs (5/83) and 0% of cats). Gastrointestinal signs were common but were not predictive of progression to neurological signs. Thus, differentiating between coral snake exposure and envenomation before the onset of neurological signs remains challenging.
Topics: Animals; Dogs; Antivenins; Retrospective Studies; Cats; Coral Snakes; Snake Bites; Cat Diseases; Elapid Venoms; Male; Female; Dog Diseases; Treatment Outcome; Venomous Snakes
PubMed: 38922141
DOI: 10.3390/toxins16060246 -
Cells Jun 2024Envenomation by the in the Western Ghats of India (particularly in the Malabar region of Kerala) and the subcontinent island nation of Sri Lanka is known to inflict...
Envenomation by the in the Western Ghats of India (particularly in the Malabar region of Kerala) and the subcontinent island nation of Sri Lanka is known to inflict devastating mortality and morbidity. Currently, bites in India are devoid of anti-venom regimens. A detailed characterization of the venom is essential to stress the need for therapeutic anti-venom. Notably, the deleterious effects of this venom on human blood cells have largely remained less explored. Therefore, in continuation of our previous study, in the present study, we envisioned investigating the effect of venom on the morphological and physiological properties of red blood cells (RBCs). The venom readily induced deleterious morphological changes and, finally, the aggregation of washed RBCs. The aggregation process was independent of the ROS and the intracellular Ca ion concentration. Confocal and scanning electron microscopy (SEM) images revealed the loss of biconcave morphology and massive cytoskeletal disarray. Crenation or serrated plasma membrane projections were evenly distributed on the surface of the RBCs. The venom did not cause the formation of methemoglobin in washed RBCs but was significantly induced in whole blood. Venom did not affect glucose uptake and Na/K -ATPase activity but inhibited glucose 6 phosphate dehydrogenase activity and decreased the fluidity of the plasma membrane. Venom-induced RBC aggregates exhibited pro-coagulant activity but without affecting platelet aggregation. In pre-incubation or co-treatment studies, none of the bioactive compounds, such as melatonin, curcumin, fisetin, berberine, and quercetin, sugars such as mannose and galactose, and therapeutic polyvalent anti-venoms (Bharat and VINS) were inhibited, whereas only N-acetylcysteine and monovalent anti-venom could inhibit venom-induced deleterious morphological changes and aggregation of RBCs. In post-treatment studies, paradoxically, none of the bioactives and anti-venoms, including N-acetylcysteine and monovalent anti-venom, reversed the venom-induced RBC aggregates.
Topics: Animals; Humans; Erythrocytes; Acetylcysteine; Crotalid Venoms; Erythrocyte Aggregation; Antivenins; Calcium; Crotalinae; Reactive Oxygen Species
PubMed: 38920625
DOI: 10.3390/cells13120994