Pathological Symptoms Research Articles

Rekayasa Genetik pada Nyamuk Penyebab Malaria: Kajian Literatur

Indonesia is a country with a heterogeneous tropical climate and is also vulnerable to the impacts of regional and global climate change. Malaria is transmitted by the Anopheles sp mosquito, the clinical and pathological symptoms of malaria are almost exclusively caused by the asexual phase of plasmodium in erythrocytes. This research uses a qualitative descriptive approach, because the data used comes from descriptions of words, with the type of library research or literature review. Library research and library searches are not only carried out as initial steps in preparing a research framework but also serve as library sources that are used as sources of research data. Search for data via Google Scholar using the keywords "genetic engineering" and "malaria mosquito" then select and eliminate data sources that are appropriate to the topic, namely genetic engineering of mosquitoes that cause malaria. The results of the literature review found that: (1) Genetic engineering is a technology that involves the manipulation of DNA molecules, which is also known as recombinant DNA technology; (2) Various terms in gene molecular manipulation techniques, such as DNA recombination, gene cloning, and gene modification; (3) Genetic engineering using basic methods, such as DNA isolation, PCR, RT-PCR, hybridization techniques, and RFLP analysis; and (4) Genetic engineering of mosquitoes can be done in several ways, namely: the sterile male technique, the distribution of mosquitoes with dominantly lethal genes, and coding genes (Gen Drives).

Structural characterization of Aspalatus linearis polysaccharide and its improving effect on acute alcoholic liver injury.

Polysaccharides from natural sources can regulate the composition of intestinal flora through the "gut-liver axis" pathway, potentially ameliorating alcoholic liver injury. Aspalathus linearis, also known as rooibos, is one such natural product that has shown promise in this regard. This study looked at the structural properties of A. linearis polysaccharide (ALP) and how well it would work to treat acute alcoholic liver impairment. This study looks at the composition of monosaccharides, functional groups, and molecular weight (Mw) of a newly discovered water-soluble polysaccharide, named ALP. The polysaccharide is composed of pyranose rings, amide groups, and sulfate groups linked by β-glycosidic linkage. It has a relative Mw of 4.30×103kDa and is composed of glucose, rhamnose, and some other monosaccharides. The study found that treating mice with the model of acute alcoholic liver disease with ALP could alleviate pathological symptoms, inhibit the release of inflammatory cytokines, and suppress indicators of oxidative stress. Experiments have shown that different doses of ALP can activate the P4502E1/Keap1-Nrf2-HO-1 signaling pathway. The regulation of inflammatory factors and downstream antioxidant enzymes occurs as a result. Based on these data, it is likely that ALP protects the liver via the "gut-liver axis" pathway by reducing oxidative stress-related damage, inflammation, and alcohol-related alterations to the gut microbiome. The results indicate that ALP mitigates injury caused by oxidative stress, inflammatory responses, and changes in the gut microbiota induced by alcohol through the "gut-liver axis" pathway, which provides protection to the liver. This provides preliminary evidence for the development of related drugs. PRACTICAL APPLICATION: Researchers extracted a polysaccharide from fresh leaves of Auricularia auricula. The polysaccharide was purified and determined to have a predominantly homogeneous molecular weight. An acute alcoholic liver damage mouse model was established, and it was concluded that the polysaccharide could ameliorate liver injury in mice through the "gut-liver axis" pathway. This novel polysaccharide can be used as an additive to develop functional foods with beneficial effects, which can positively impact the daily maintenance of consumers.

Validation of the eating pathology symptoms inventory (EPSI) in Swedish adolescents

BackgroundEating disorders (ED) are associated with symptoms across body image, disordered eating, and exercise-related domains, and while predominantly affecting females, ED in males is also a significant concern. However, popular self-report methods insufficiently capture male presentations. This study aimed (1) to validate the first Swedish translation of the Eating Pathology Symptoms Inventory (EPSI), which was designed to overcome limitations in previous measures, and (2) compare genders gender-specific manifestations of eating pathology, depression, and anxiety in Swedish high-school students.MethodsParticipants were 359 high-school students (47% males) aged 17.0 years (range 15–21).ResultsConfirmatory factor analysis and correlation patterns showed support for the 8-factor structure and convergent validity, but poorer discriminant validity may suggest caution in interpreting single scales as evidence of ED pathology. Gender comparisons were broadly consistent with previous research.Conlusions: The Swedish EPSI may be used to asses ED symptoms, but caution is suggested in interpreting some scales in isolation as indicative of ED pathology.

Effects of Low-Lipid Diets on Growth, Haematology, Histology and Immune Responses of Parr-Stage Atlantic Salmon (Salmo salar).

Lipids in fish diets provide energy and play important roles in immunity and metabolism. Atlantic salmon, a species that migrates from freshwater to seawater, requires high energy, especially during smoltification. Juvenile teleosts have low lipid requirements, and a high dietary lipid content is known to have negative effects on their growth and digestion. Therefore, this study evaluated the effect of two commercial rainbow trout feeds (low-lipid, 13.41% and 14.6%) on the growth and immune responses of early parr-stage Atlantic salmon compared to commercial salmon feed (high-lipid, 29.52%). Atlantic salmon parr (weight: 14.56 ± 2.1 g; length: 11.23 ± 0.44 cm) were randomly divided into three groups and fed either one of two commercial rainbow trout feeds (RTF1 and RTF2) or the commercial salmon feed (ASF) for 12 weeks. At the end of the feeding trial, growth, haematology, histology and gene expression analyses were performed. There were no significant differences in weight gain rates or feed efficiency between the groups (p > 0.05). Superoxidate dismutase, glutathione peroxidase, lysozyme and immunoglobulin M activities were not different among the experimental groups (p > 0.05). A histological examination of the liver and intestinal tissues showed no pathological symptoms of inflammatory response or lipid accumulation in any of the groups. In an intestinal transcriptome analysis using RNA-seq, the expression levels of several genes linked to lipids, immune-related proteins, cytokines and chemokines did not differ significantly between the groups (p > 0.05). Commercial rainbow trout feed with low lipid content has no clear negative impact on the development of Atlantic salmon during the early parr stage (14.5 to 39.6 g). This study provides basic information for the development of economical feed for early parr-stage Atlantic salmon.

A Novel Therapy for Polymyalgia Rheumatica Dopaminergic Drugs

Objectives: There is good anecdotal support for the concept that most chronic disorders involve increased cellular permeability allowing irritants to infuse into various organs either causing pain or physiological disruption of organ function. There is support for the concept that the large majority of these disorders, despite recalcitrance to standard therapy for that disorder, will demonstrate impressive relief of these various pathological symptoms following treatment with drugs that release dopamine from sympathetic nerve fibers, especially, but not exclusively limited to dextroamphetamine sulfate. Dopamine is known to decrease cellular permeability. The various disorders effecting almost every organ system of the human body fall under the umbrella term of the increased cellular permeability syndrome. Presented here in the first case of polymyalgia rheumatica in a male who was unable to tolerate the dosage of glucocorticoids that may have provided significant pain relief because of psychogenic side effects, who quickly responded to dextroamphetamine sulfate without any side effects.

Integrating metabolomics and network pharmacology analysis to explore mechanism of Pueraria lobata against pulmonary fibrosis: Involvement of arginine metabolism pathway

Ethnopharmacological relevancePueraria lobata (Willd.) Ohwi is a typical medicinal and edible plant with a long application history in China and Southeast Asia. As a widely used traditional medicine, P. lobata exhibits the properties of anti-inflammatory, antipyretic, antioxidant, relieving cough and asthma. Particularly, the increasing evidence indicates that the P. lobata has the therapeutic effect on fibrotic-related diseases in terms of metabolic regulation. However, the mechanisms of P. lobata on pulmonary fibrosis (PF) has not been thoroughly explored. Aim of the studyThis study aimed to explore the effect of arginine metabolites of P. lobata against PF model by integrating metabolomics and network pharmacology analysis. It might provide a new idea for the target finding of P. lobata anti-pulmonary fibrosis. Materials and methodsIn this study, the Sprague Dawley (SD) rats were randomly divided into five experimental groups: saline-treated control group, bleomycin-induced fibrosis group, prednisolone acetate group, P. lobata 3.2 g/kg group and P. lobata 6.4 g/kg group. The therapeutic effect of P. lobata on bleomycin-induced PF in rats was evaluated by clinical symptoms such as lung function, body weight, hematoxylin eosin staining (HE), Masson staining and hydroxyproline assay. Next, the plasma metabolomics analysis was carried out by LC-MS to explore the pathological differences between the group of control, PF and P. lobata-treated rats. Then, the network pharmacology study coupled with experimental validation was conducted to analysis the results of metabolic research. We constructed the “component-target-disease” network of P. lobata in the treatment of PF. In addition, the molecular docking method was used to verify the interaction between potential active ingredients and core targets of P. lobata. Finally, we tested NOS2 and L-OT in arginine-related metabolic pathway in plasma of the rats by enzyme-linked immunosorbent assay (ELISA). Real-time PCR was performed to observe the level of TNF-α mRNA and MMP9 mRNA. And we tested the expression of TNF-α and MMP9 by Western blot analysis. ResultsOur findings revealed that P. lobata improved lung function and ameliorated the pathological symptoms, such as pathological damage, collagen deposition, and body weight loss in PF rats. Otherwise, the plasma metabolomics were employed to screen the differential metabolites of amino acids, lipids, flavonoids, arachidonic acid metabolites, glycoside, etc. Finally, we found that the arginine metabolism signaling mainly involved in the regulating of P. lobata on the treatment of PF rats. Furtherly, the network pharmacology predicted that the arginine metabolism pathway was contained in the top 20 pathways. Next, we integrated metabolomics and network pharmacology that identified NOS2, MMP9 and TNF-α as the P. lobata regulated hub genes by molecular docking. Importantly, it indicated a strong affinity between the puerarin and the NOS2. P. lobata attenuated TNF-α, MMP-9 and NOS2 levels, suppressed TNF-α and MMP-9 protein expression, and decreased L-OT and NOS2 content in PF rats. These results indicated that the effects of P. lobata may ameliorated PF via the arginine metabolism pathway in rats. Therefore, P. lobata may be a potential therapeutic agent to ameliorated PF. ConclusionIn this work, we used metabolomics and network pharmacology to explore the mechanisms of P. lobata in the treatment of PF. Finally, we confirmed that P. lobata alleviated BLM-induced PF in rats by regulating arginine metabolism pathway based on reducing the L-OT and NOS2-related signal molecular. The search for the biomarkers finding of arginine metabolism pathway revealed a new strategy for P. lobata in the treatment of PF.

Improving the diagnostic performance of the neural network for COVID-19VN via weight assignment to pathological symptoms

In this article, we present how to create a database of Covid-19 diseases at National Hospital of Tropical Diseases (called the CovidVN database) and then develop a learning neural network based on this database to diagnose this disease. The CovidVN Database is built based on the processing of real diagnostic test results of Covid-19 patients with a large number of samples and in accordance with the structure of the Israeli Health System Covid-19 disease database (called COVIDIsr Database). Then two MLP Artificial Neural Networks corresponding to these two databases will be developed using the Deep Learning Toolbox of MATLAB software; the results of training these networks and their accuracy are compared with each other to assess the relative quality of the CovidVN database. Other, the paper presents the method of assigning weight corresponding to pathological symptoms for network input parameters. The results showed that the weighting of input attributes corresponding to the pathological symptoms is significant.

Long Non-Coding RNA Analysis: Severe Pathogenicity in Chicken Embryonic Visceral Tissues Infected with Highly Virulent Newcastle Disease Virus-A Comparison to the Avirulent Vaccine Virus.

There are significant variations in pathogenicity among different virulent strains of the Newcastle disease virus (NDV). Virulent NDV typically induces severe pathological changes and high mortality rates in infected birds, while avirulent NDV usually results in asymptomatic infection. Currently, the understanding of the specific mechanisms underlying the differences in host pathological responses and symptoms caused by various virulent NDV strains remains limited. Long non-coding RNA (lncRNA) can participate in a range of biological processes and plays a crucial role in viral infection and replication. Therefore, this study employed RNA-Seq to investigate the transcriptional profiles of chicken embryos' visceral tissues (CEVTs) infected with either the virulent NA-1 strain or avirulent LaSota strain at 24 hpi and 36 hpi. Using bioinformatic methods, we obtained a total of 2532 lncRNAs, of which there were 52 and 85 differentially expressed lncRNAs at 24 hpi and 36 hpi, respectively. LncRNA analysis revealed that the severe pathological changes and symptoms induced by virulent NDV infection may be partially attributed to related target genes, regulated by differentially expressed lncRNAs such as MSTRG.1545.5, MSTRG.14601.6, MSTRG.7150.1, and MSTRG.4481.1. Taken together, these findings suggest that virulent NDV infection exploits the host's metabolic resources and exerts an influence on the host's metabolic processes, accompanied by excessive activation of the immune response. This impacts the growth and development of each system of CEVTs, breaches the blood-brain barrier, inflicts severe damage on the nervous system, and induces significant lesions. These observations may be attributed to variations in pathology. Consequently, novel insights were obtained into the intricate regulatory mechanisms governing NDV and host interactions. This will aid in unraveling the molecular mechanisms underlying both virulent and avirulent forms of NDV infection.

ВЛИЯНИЕ ГИПОТЕНЗИВНЫХ ПРЕПАРАТОВ В ПОСЛЕОПЕРАЦИОННОМ ПЕРИОДЕ У ПАЦИЕНТОВ С ПСЕВДОЭКСФОЛИАТИВНЫМ СИНДРОМОМ НА ФОНЕ ОСЛОЖНЕННОЙ КАТАРАКТЫ

In modern surgery of complicated cataracts, an important factor is the preservation of visual functions with minimal costs. The surgeon’s experience and modern technology, which makes it possible to identify hidden symptoms of certain pathologies at the diagnostic stage, allows for a favorable completion of surgery with minimal intraoperative complications. This article shows the approach and observations of patients at risk of increasing eye pressure in the postoperative period due to the anatomical structures of the eye (in these cases, patients with open-angle glaucoma) to antihypertensive drugs. 131 patients (134 eyes) with various signs of pseudoexfoliation syndrome participated in the observation. Before planned surgery for complicated cataracts, all patients underwent ophthalmological diagnostics, medical history, and laboratory tests according to generally accepted methods. All operations were performed by the same surgeon. Cataract surgery was performed according to the standard technique (Phaco + intraocular lens) through a 2.2 mm incision, two 1.2 mm paracentesis, but for some patients other components of surgical interventions were added. In the observation groups, for better fixation and a lower percentage of complications in long-term follow-up periods, RPR, T-19, Myol were implanted in 27.7%. A large percentage of 34% were implanted with the HO Acrylic IOL model lens, which requires a 2.2 mm corneal incision. In observation groups 2 and 3, 32.5 and 31.8% preferred lenses to the Acrysoft IQ model. And in 32.5% and 13.6%, respectively, the AFY model. The choice of the method of surgical intervention, as well as the model of intraocular lenses, made it possible to predict the long-term postoperative period with less toxicity for the patient’s condition. No intraoperative complications were observed; the administration of antihypertensive drops, both in combination and in monotherapy in the early stages of the postoperative period, allowed maintaining eye pressure within normal limits in all observation groups.

Exploring the underlying mechanisms of enteritis impact on golden pompano (Trachinotus ovatus) through multi-omics analysis

Enteritis posed a significant health challenge to golden pompano (Trachinotus ovatus) populations. In this research, a comprehensive multi-omics strategy was implemented to elucidate the pathogenesis of enteritis by comparing both healthy and affected golden pompano. Histologically, enteritis was characterized by villi adhesion and increased clustering after inflammation. Analysis of the intestinal microbiota revealed a significant increase (P < 0.05) in the abundance of specific bacterial strains, including Photobacterium and Salinivibrio, in diseased fish compared to the healthy group. Metabolomic analysis identified 5479 altered metabolites, with significant impacts on terpenoid and polyketide metabolism, as well as lipid metabolism (P < 0.05). Additionally, the concentrations of several compounds such as calcitetrol, vitamin D2, arachidonic acid, and linoleic acid were significantly reduced in the intestines of diseased fish post-enteritis (P < 0.05), with the detection of harmful substances such as Efonidipine. In transcriptomic profiling, enteritis induced 68 upregulated and 73 downregulated genes, predominantly affecting steroid hormone receptor activity (P < 0.05). KEGG pathway enrichment analysis highlighted upregulation of SQLE and CYP51 in steroidogenesis, while the HSV-1 associated MHC1 gene exhibited significant downregulation. Integration of multi-omics results suggested a potential pathogenic mechanism: enteritis may have resulted from concurrent infection of harmful bacteria, specifically Photobacterium and Salinivibrio, along with HSV-1. Efonidipine production within the intestinal tract may have blocked certain calcium ion channels, leading to downregulation of MHC1 gene expression and reduced extracellular immune recognition. Upregulation of SQLE and CYP51 genes stimulated steroid hormone synthesis within cells, which, upon binding to G protein-coupled receptors, influenced calcium ion transport, inhibited immune activation reactions, and further reduced intracellular synthesis of anti-inflammatory substances like arachidonic acid. Ultimately, this cascade led to inflammation progression, weakened intestinal peristalsis, and villi adhesion. This study utilized multi-level omics detection to investigate the pathological symptoms of enteritis and proposed a plausible pathogenic mechanism, providing innovative insights into enteritis verification and treatment in offshore cage culture of golden pompano.

Inhibition of LSD1 via SP2509 attenuated the progression of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic autoimmune disease characterized by synovial hyperplasia, pannus formation, and cartilage and bone destruction. Lysine-specific demethylase 1 (LSD1), an enzyme involved in transcriptional regulation, has an unclear role in synovial inflammation, fibroblast-like synoviocytes migration, and invasion during RA pathogenesis. In this study, we observed increased LSD1 expression in RA synovial tissues and in TNF-α-stimulated MH7A cells. SP2509, an LSD1 antagonist, directly reduced LSD1 expression and reversed the elevated levels of proteins associated with inflammation, apoptosis, proliferation, and autophagy induced by TNF-α. Furthermore, SP2509 inhibited the migratory capacity of MH7A cells, which was enhanced by TNF-α. In CIA models, SP2509 treatment ameliorated RA development, reducing the expression of pro-inflammatory cytokines and alleviating joint pathological symptoms. These findings underscore the significance of LSD1 in RA and propose the therapeutic potential of SP2509.

Effects of transcranial direct current stimulation (tDCS) on positive and negative symptoms in patients with schizophrenia

Effects of transcranial direct current stimulation (tDCS) on positive and negative symptoms in patients with schizophrenia

Biocontrol potential of some bacterial and fungal isolates against the terrestrial snail, Monacha obstructa, evaluating their laboratory and field efficiency

BackgroundThe land snail Monacha obstructa, commonly known as the glassy clover snail, poses a significant threat to crops, causing substantial damage in agriculture and horticulture. It particularly thrives in regions of Egypt, where it can reproduce rapidly, leading to substantial population increases and consequent damage. This study aimed to perform laboratory experiments and field trials to assess the effectiveness of bacterial (Bacillus thuringiensis) and fungal (Metarhizium anisopliae and Trichoderma harzianum) isolates, as well as methomyl, a carbamate compound approved by the Ministry of Agriculture in Egypt against the terrestrial snails. Various methods including contact and leaf dipping as well as baiting techniques were applied under both laboratory and field conditions, using spray and baiting techniques.ResultsBacillus thuringiensis (Bt) and M. anisopliae isolates showed the most effective results outcomes in comparison with methomyl against M. obstructa. Out of all the application approaches tested, the residual film (contact) technique of these microorganisms proved to be the most potent, with LC50 values of 6.49 × 106 cells/ml Bt (after 14 days), 1.24 × 108 and 1.49 × 108 spores/ml (M. anisopliae, T. harzianum, respectively), after 21 days and 620 ppm, for methomyl after 7 days of treatments. Besides, the findings demonstrated that Bt exhibited the highest success rate in decreasing the number of snails in the field. It was also observed that pathological symptoms increased as the duration of exposure increased, and the snails ceased to feed and showed a noticeable decline in their activity. A slimy, almost tan-like substance coated the exterior of their shells for Bt, and part of the soft body came out of the shell for M. anisopliae. In the case of T. harzianum, fungus hypha growth took on a white color formed inside the shell, and in addition, a black substance formed on the mouth of the shell.ConclusionsThe gathered data revealed that Bt and M. anisopliae effectively combatted the terrestrial snail, making them viable options in integrated pest control as substitutes for pesticides.

The Review of Ophthalmic Symptoms in COVID-19.

The COVID-19 pandemic caused by SARS-CoV-2 had a significant impact on the health of the global human population, affecting almost every human organ, including the organ of vision. Research focus on understanding the pathophysiology, identifying symptoms and complications of the disease. Eye-related pathologies are important foci of research due to the potential for direct impact of the virus. Ophthalmologists around the world are reporting various symptoms of eye infections and ocular pathologies associated with SARS-CoV-2. The review of ophthalmic symptoms was conducted to help physicians of various specialties recognize possible ophthalmic manifestations of this viral disease. A literature review was conducted from January 2020 to July 2023 in the PubMed, MEDLINE, Science Direct, Scopus, Scielo and Google Scholar databases. The review of the literature showed that conjunctivitis is the most common ophthalmic symptom observed during the course of COVID-19 and can occur at any stage of the disease. Changes in the eye may result from the direct effect of the virus, immune response, prothrombotic states, comorbidities, and medications used. Symptoms related to the organ of vision can be divided into: changes affecting the protective apparatus of the eye, the anterior eye segment, the posterior eye segment, neuro-ophthalmic, and orbital changes. Ocular symptoms may suggest COVID-19 infection or appear several weeks after recovery. Following COVID-19 vaccinations, a diverse range of ophthalmic symptoms was observed in various locations and at different times, mirroring the ocular symptoms experienced throughout the course of the COVID-19 illness. It is important for physicians of all specialties to be aware of possible potential connections between eye diseases and SARS-CoV-2, in order to effectively diagnose and treat patients.

Dermatomyositis

Dermatomyositis (DM) is distinguished from other idiopathic inflammatory myopathies by the characteristic skin rashes, muscle pathology, and muscle symptoms. Five myositis-specific autoantibodies have been identified in DM, and the correlation between each antibody and the clinical picture is clear. Pathological analysis has also identified DM as a type I interferonopathy of the skeletal muscle. Consideration of treatment strategies requires careful evaluation of muscle strength, systemic inflammatory findings, muscle pathology, muscle imaging, and complications such as malignancy and interstitial lung disease. Corticosteroids are administered as first-line treatment, and immunosuppressive agents and intravenous immunoglobulins are employed as important second-line treatments. Some patients exhibit resistance to these therapies. Currently, treatment strategies for refractory cases are not well established, necessitating further development of treatment methods.

ANGPTL2 knockdown induces autophagy to relieve alveolar macrophage pyroptosis by reducing LILRB2-mediated inhibition of TREM2.

Acute lung injury (ALI) is featured with a robust inflammatory response. Angiopoietin-like protein 2 (ANGPTL2), a pro-inflammatory protein, is complicated with various disorders. However, the role of ANGPTL2 in ALI remains to be further explored. The mice and MH-S cells were administrated with lipopolysaccharide (LPS) to evoke the lung injury invivo and invitro. The role and mechanism of ANGPTL was investigated by haematoxylin-eosin, measurement of wet/dry ratio, cell count, terminal deoxynucleotidyl transferase deoxyuridine triphosphate (dUTP) nick end labeling, reverse transcription quantitative polymerase chain reaction, immunofluorescence, enzyme-linked immunosorbent assay, detection of autophagic flux and western blot assays. The level of ANGPTL2 was upregulated in lung injury. Knockout of ANGPTL2 alleviated LPS-induced pathological symptoms, reduced pulmonary wet/dry weight ratio, the numbers of total cells and neutrophils in BALF, apoptosis rate and the release of pro-inflammatory mediators, and modulated polarization of alveolar macrophages in mice. Knockdown of ANGPTL2 downregulated the level of pyroptosis indicators, and elevated the level of autophagy in LPS-induced MH-S cells. Besides, downregulation of ANGPTL2 reversed the LPS-induced the expression of leukocyte immunoglobulin (Ig)-like receptor B2 (LILRB2) and triggering receptor expressed on myeloid cells 2 (TREM2), which was reversed by the overexpression of LILRB2. Importantly, knockdown of TREM2 reversed the levels of autophagy- and pyroptosis-involved proteins, and the contents of pro-inflammatory factors in LPS-induced MH-S cells transfected with si ANGPTL2, which was further inverted with the treatment of rapamycin. Therefore, ANGPTL2 silencing enhanced autophagy to alleviate alveolar macrophage pyroptosis via reducing LILRB2-mediated inhibition of TREM2.

Novel 1,2,3-triazoles as Inhibitors of the Toxic Effects of the Venom of the Snake Lachesis muta muta

Background:: Snakebites are a worldwide health problem and produce pathological symptoms, such as hemorrhage, tissue necrosis, blood coagulation disorder, edema, and death. Although serum therapy protects victims from death, it does not prevent amputation of the affected limb. Therefore, alternative treatments deserve attention. Objective:: To test a new series of twelve disubstituted triazoles, TRI 02, TRI 03, TRI 04, TRI 05, TRI 07, TRI 08, TRI 09, TRI 11, TRI 14, TRI 16, TRI 17, and TRI 18 against the hemorrhagic, edematogenic, hemolytic, coagulant, and proteolytic activities of Lachesis muta muta venom. Methods:: The derivatives were incubated with L. muta venom (incubation protocol), then the toxic activities were measured. L. m. muta venom was injected before (treatment protocol) or after (prevention protocol) the derivatives. Results:: Most of the derivatives inhibited the proteolytic and hemolytic activity of L. m. muta venom, but only TRI 17 inhibited coagulation activity. The derivatives TRI 03, TRI 05, TRI 07, TRI 14, and TRI 17 inhibited hemorrhage, while TRI 07, TRI 08, and TRI 16 inhibited edema. The derivatives TRI 03, TRI 07, and TRI 11 inhibited hemorrhage whether they were administered before or after L. m. muta venom. According to in silico tool, TRI 03, TRI 04, TRI 07, TRI 08, TRI 09, TRI 16, TRI 17, and TRI 18 were not toxic. The derivatives did not violate Lipinksi’s rule of five. Conclusion:: These triazoles serve as molecules able to improve the treatment of L. m. muta envenoming.

Eating disorder symptoms and diagnoses in adults with celiac disease

Introduction: Treatment for Celiac Disease (CeD) includes strict adherence to a Gluten-Free Diet (GFD) which may result in preoccupation with food choice, unwanted weight gain, and body dissatisfaction. Objective: To determine frequency of Eating Disorder (ED) diagnoses and symptoms in adults with CeD. Method: The Eating Disorder Diagnostic Scale (EDDS-DSM-5) and the Eating Pathology Symptoms Inventory (EPSI) were administered in a cross-sectional study of 50 adults with biopsy-confirmed CeD on a GFD for &gt;1 year attending their routine clinic visits. Results: Based on the EDDS, one participant met criteria for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of binge eating disorder and four met criteria for possible diagnosis of Other Specified Feeding and Eating Disorders; none had previously been diagnosed with an ED. EDDS symptom scores were lower (i.e., better) than established cut-points, yet females scored higher than males when asked if they felt fat (p&lt;0.001), feared weight gain (p&lt;0.001), and felt undue influence of weight/ shape (p=0.034). EPSI scores were lower (i.e., better) than normative values, yet females scored significantly higher than males on body dissatisfaction (p&lt;0.001), cognitive restraint (p=0.011), and purging (p=0.044) subscales. Conclusion: Although disordered eating behaviors and weight/ shape concerns were apparent, only one patient met full criteria for an ED diagnosis. The EDDS and EPSI may be useful in screening for comorbidity among adults with CeD; however, clinical assessment is needed to assign a DSM-5 ED diagnosis.

Safranal exerts a neuroprotective effect on Parkinson's disease with suppression of NLRP3 inflammation activation.

Parkinson's disease (PD) is a common central nervous system neurodegenerative disease. Neuroinflammation is one of the significant neuropathological hallmarks. As a traditional Chinese medicine, Safranal exerts anti-inflammatory effects in various diseases, however, whether it plays a similar effect on PD is still unclear. The study was to investigate the effects and mechanism of Safranal on PD. The PD mouse model was established by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine MPTP firstly. Next, the degree of muscle stiffness, neuromuscular function, motor retardation and motor coordination ability were examined by observing and testing mouse movement behavior. Immunofluorescence staining was used to observe the expression of tyrosine hydroxylase (TH). The dopamine (DA) content of the striatum was detected by High-performance liquid chromatography (HPLC). The expression of TH and NLRP3 inflammasome-related markers NLRP3, IL-1β, and Capase-1 were detected by Real-time Polymerase Chain Reaction (qRT-PCR) and western blotting (WB) respectively. Through behavioral testing, Parkinson's mouse showed a higher muscle stiffness and neuromuscular tension, a more motor retardation and activity disorders, together with a worse motor coordination compared with sham group. Simultaneously, DA content and TH expression in the striatum were decreased. However, after using Safranal treatment, the above pathological symptoms of Parkinson's mouse all improved compared with Safranal untreated group, the DA content and TH expression were also increased to varying degrees. Surprisingly, it observed a suppression of NLRP3 inflammation in the striatum of Parkinson's mouse. Safranal played a neuroprotective effect on the Parkinson's disease and its mechanism was related to the inhibition of NLRP3 inflammasome activation.

Manual acupuncture ameliorates inflammatory pain by upregulating adenosine A3 receptor in complete Freund’s adjuvant-induced arthritis rats

BackgroundAdenosine A3 receptor (A3R) exerts analgesic, anti-inflammatory, and anti-nociceptive effects. In this study, we determined the analgesic mechanism of manual acupuncture (MA) in rats with complete Freund's adjuvant (CFA)-induced arthritis and explored whether MA ameliorates inflammation in these rats by upregulating A3R. MethodsSixty Sprague Dawley (SD) rats were randomly divided into the following groups: Control, CFA, CFA + MA, CFA + sham MA, CFA + MA + DMSO, CFA + MA + IB-MECA, and CFA + MA + Reversine groups. The arthritis rat model was induced by injecting CFA into the left ankle joints. Thereafter, the rats were subjected to MA (ST36 acupoint) for 3 days. The clinical indicators paw withdrawal latency (PWL), paw withdrawal threshold (PWT), and open field test (OFT) were used to determine the analgesic effect of MA. In addition, to explore the effect of A3R on inflammation after subjecting arthritis rats to MA, IB-MECA (A3R agonist) and Reversine (A3R antagonist) were injected into ST36 before MA. ResultsMA ameliorated the pathological symptoms of CFA-induced arthritis, including the pain indicators PWL and PWT, number of rearing, total ambulatory distance, and activity trajectory. Furthermore, after MA, the mRNA and protein expression of A3R was upregulated in CFA-induced arthritis rats. In contrast, the protein levels of TNF-α, IL-1β, Rap1, and p-p65 were downregulated after MA. Interestingly, the A3R agonist and antagonist further downregulated and upregulated inflammatory cytokine expression, respectively, after MA. Furthermore, the A3R antagonist increased the degree of ankle swelling after MA. ConclusionMA can alleviate inflammatory pain by inhibiting the NF-κB signaling pathway via upregulating A3R expression of the superficial fascia of the ST36 acupoint site in CFA-induced arthritis rats.