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المؤلفون: Tobias Schmidt, Fredrik Kahn, Robin Kahn
المصدر: Journal of Leukocyte Biology. 112:491-498
مصطلحات موضوعية: Lipopolysaccharides, CD40, biology, Chemistry, Monocyte, medicine.medical_treatment, Immunology, Ascorbic Acid, Cell Biology, Pharmacology, CD16, Ascorbic acid, medicine.disease, Monocytes, Sepsis, medicine.anatomical_structure, Cytokine, biology.protein, medicine, Cytokines, Humans, Immunology and Allergy, Tumor necrosis factor alpha, CD163
الوصف: Sepsis manifests due to the host’s dysregulated immune response to an infection. High dose ascorbic acid (AA) has emerged as a potential treatment of sepsis, yet little is known regarding how ascorbic acid influences the immune system in sepsis, such as monocytes. The objective of this study is to investigate the effects of high dose AA on monocyte polarization and cytokine production in vitro.Monocytes were isolated from healthy donors (n=6) and polarized in vitro for 48hrs using lipopolysaccharide (LPS) and lipoteichoic acid (LTA). Polarization was confirmed by surface marker expression using flow cytometry. In parallel, monocytes from septic patients (n=3) were analyzed for polarization markers as a comparison to the in vitro polarization. The effect of AA on monocyte polarization was evaluated. Finally, monocytes were analyzed for cytokine production of TNF and IL-8 by intracellular staining.Both LPS and LTA induced polarization in healthy monocytes in vitro, with increased expression of both pro- (CD40 and PDL1, pThus, AA attenuates cytokine production and upregulation of anti-, but not pro-inflammatory related markers in LPS or LTA polarized monocytes. This study provides important insight into the effects of high dose AA on monocytes, and potential implications in sepsis.Summary sentenceAscorbic acid inhibits production of IL-8, TNF, and upregulation of the polarization markers CD16 and CD163 in LPS or LTA polarized monocytes in vitro.
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المؤلفون: Géraldine Bart, Benoit Le Goff, Laurie Charret, Grégoire Cormier, David Boutoille, Emmanuelle Dernis, Christelle Darrieutort-Laffite, Emmanuel Hoppe
المصدر: Journal of Antimicrobial Chemotherapy. 76:3029-3032
مصطلحات موضوعية: Male, 0301 basic medicine, Microbiology (medical), medicine.medical_specialty, Bursitis, medicine.drug_class, Olecranon, 030106 microbiology, Antibiotics, medicine.disease_cause, Septic bursitis, 03 medical and health sciences, 0302 clinical medicine, Internal medicine, Antibiotic therapy, Elbow Joint, medicine, Humans, Pharmacology (medical), Olecranon Process, Pharmacology, 030222 orthopedics, Streptococcus, business.industry, Bacterial Infections, Middle Aged, medicine.disease, Comorbidity, Anti-Bacterial Agents, Infectious Diseases, medicine.anatomical_structure, Cellulitis, Female, business
الوصف: Background No current guidelines are available for managing septic bursitis (SB). Objectives To describe the clinical characteristics and management of olecranon and prepatellar SB in five French tertiary care centres. Methods This is a retrospective observational multicentre study. SB was diagnosed on the basis of positive cultures of bursal aspirate. In the absence of positive bursal fluid, the diagnosis came from typical clinical presentation, exclusion of other causes of bursitis and favourable response to antibiotic therapy. Results We included 272 patients (median age of 53 years, 85.3% male and 22.8% with at least one comorbidity). A microorganism was identified in 184 patients (67.6%), from bursal fluids in all but 4. We identified staphylococci in 135 samples (73.4%), streptococci in 35 (19%) and 10 (5.5%) were polymicrobial, while 43/223 bursal samples remained sterile (19.3%). Forty-nine patients (18%) were managed without bursal fluid analysis. Antibiotic treatment was initially administered IV in 41% and this route was preferred in case of fever (P = 0.003) or extensive cellulitis (P = 0.002). Seventy-one (26%) patients were treated surgically. A low failure rate was observed (n = 16/272, 5.9%) and failures were more frequent when the antibiotic therapy lasted Conclusions Despite variable treatments, SB resolved in the majority of cases even when the treatment was exclusively medical. The success rate was equivalent in the non-surgical and the surgical management groups. However, a treatment duration of
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dafaeae5cf13b4a9e6db087760bf84c9
https://doi.org/10.1093/jac/dkab265 -
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المصدر: Toxicol Res (Camb)
مصطلحات موضوعية: Paper, 0301 basic medicine, medicine.medical_specialty, Cerebellum, Hyperhomocysteinemia, Homocysteine, Health, Toxicology and Mutagenesis, Toxicology, medicine.disease_cause, Lipid peroxidation, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, heterocyclic compounds, chemistry.chemical_classification, 030102 biochemistry & molecular biology, business.industry, Glutathione peroxidase, medicine.disease, Endocrinology, medicine.anatomical_structure, chemistry, Toxicity, business, Quercetin, 030217 neurology & neurosurgery, Oxidative stress
الوصف: Homocysteine (Hcy) is an excitatory amino acid that contains thiol group and derives from the methionine metabolism. It increases vulnerability of the neuronal cells to excitotoxic and oxidative damage. This study aimed to investigate the hyperhomocysteinemia (hHcy) effects on rat cerebellum and the possible protective role of quercetin administration in Hcy-treated rats, using behavioral and biochemical analyzes. To this end, the adult male rats were divided randomly into the control group that received vehicle, Hcy group received Hcy (400 μg/kg), Hcy + Que group received Hcy + quercetin (50 mg/kg), quercetin group received quercetin for 14 days. On Day 14 after the final treatment, lipid peroxidation level, the superoxide dismutase (SOD), and glutathione peroxidase (GPx) activities were evaluated in the cerebellum. After completion of treatment, the rat’s performance on rotarod and locomotor activity was evaluated. The results showed that Hcy treatment elicited cerebellar lipid peroxidation, impaired locomotor activity and increased latency to fall on the rotarod. Quercetin failed to attenuate significantly motoric impairment, increased significantly the cerebellar lipid peroxidation and GPx activity in the Hcy + Que group. Our results suggest that Hcy induced cerebellar toxicity and quercetin had no significant protective effects against Hcy toxicity in the cerebellum of adult rats.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::32bc3153b6bdca98ddc8ecfdaf5bbd9d
https://doi.org/10.1093/toxres/tfab065 -
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المؤلفون: Runzhi Huang, Jianxuan Gao, Wang Zhou, Huabin Yin, Ziheng Wei, Fuyan Liu, Jiali Jin, Na Ta, Zhengyan Chang, Dianwen Song, Jun Lin, Xiaowen Xu, Tong Meng, Zongqiang Huang
المصدر: Neuro Oncol
مصطلحات موضوعية: musculoskeletal diseases, Cancer Research, Carcinogenesis, Cell, Biology, medicine.disease_cause, Osteoclast, Chordoma, Tumor Microenvironment, medicine, Animals, Humans, Epigenetics, Cell Proliferation, Gene knockdown, Cell Cycle, Mesenchymal stem cell, medicine.disease, Chromatin, Cell Transformation, Neoplastic, medicine.anatomical_structure, Oncology, Basic and Translational Investigations, Cancer research, Neurology (clinical)
الوصف: Background Chordoma is a rare mesenchymal malignancy, with a high recurrence rate and unclear tumorigenic mechanism. Genetic alterations, epigenetic regulators, and chromatin spatial organization play crucial roles in the initiation and progression of chordoma. In the current study, we aim to uncover the novel therapeutical targets for chordoma via using integrated multi-omics analysis. Methods The RNA-sequencing (RNA-seq), assay for transposable accessible chromatin by high-throughput sequencing (ATAC-seq), and Hi-C were performed between chordoma and human nucleus pulposus (HNP), along with imageological examination and clinical information. The expressions of identified targets were validated by clinical samples and their functions were further evaluated by cell and animal experiments via gene knockdown and inhibitors. Results The integrated multi-omics analysis revealed the important roles of bone microenvironment in chordoma tumorigenesis. By comparing the hierarchical structures, CA2 (carbonic anhydrase II) and THNSL2 (threonine synthase-like 2) were identified in the switched compartments, cell-specific boundaries, and loops. Additionally, CA2 was highly expressed in chordoma but barely found in HNP. The cell growth and migration of chordoma cells were dramatically suppressed via inhibition of CA2 either with genetic deletion or pharmaceutical treatment with Dorzolamide HCl. Furthermore, Dorzolamide HCl also regulated the bone microenvironment by blocking the osteoclast differentiation of bone marrow monocytes. Conclusion This study uncovers the roles of bone microenvironment in the chordoma tumorigenesis and identifies CA2 as a novel therapeutic target for chordoma. Besides, our findings suggest Dorzolamide HCl as a promising therapeutic option for chordoma.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d08cfc1b8ba9a18f970991318a0d53c3
https://doi.org/10.1093/neuonc/noab156 -
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المؤلفون: Zhiming Zhu, Xiaowen Bao, Chaoxing Ren, Bo Ma, Jun Tang, Youli Xi, Jie Zhang, Yu Bai, Xiaowei Zhou, Nan Zhang, Qi Zhang
المصدر: Journal of Pharmacy and Pharmacology. 73:1218-1229
مصطلحات موضوعية: Male, Src Homology 2 Domain-Containing, Transforming Protein 1, Inflammasomes, medicine.medical_treatment, Intraperitoneal injection, Pharmaceutical Science, Pharmacology, Diet, High-Fat, Kidney, medicine.disease_cause, Diabetes Mellitus, Experimental, Diabetic nephropathy, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Fibrosis, NLR Family, Pyrin Domain-Containing 3 Protein, medicine, Animals, Diabetic Nephropathies, Blood urea nitrogen, 030304 developmental biology, Inflammation, Mice, Inbred ICR, 0303 health sciences, Creatinine, Dioscorea, Plant Extracts, business.industry, Caspase 1, Streptozotocin, medicine.disease, Oxidative Stress, medicine.anatomical_structure, chemistry, 030220 oncology & carcinogenesis, business, Oxidative stress, Phytotherapy, Signal Transduction, medicine.drug
الوصف: Objectives Diabetic nephropathy (DN) is a severe diabetic complication. Dioscorea zingiberensis (DZ) possesses excellent pharmacological properties with lower toxicity. The purpose of this study was to investigate the efficacy and mechanism of DZ in DN. Methods DN was established by the high-fat diet combining intraperitoneal injection of streptozotocin in mice. The DZ (125 and 250 mg/kg/day) were intragastrical administered for 8 consecutive weeks. After treatment, blood, urine and kidney tissue were collected for biological detection, renal morphology, fibrosis and molecular mechanism research, respectively. Key findings This study has shown that DZ significantly ameliorated kidney hypertrophy, renal structural damage and abnormal function of the kidney indicators (creatinine, urinary protein and blood urea nitrogen). Further molecular mechanism data suggested that the NLRP3/Cleaved-caspase-1 signal pathway was remarkably activated in DN, and DZ treatment reversed these changes, which indicated that it effectively attenuated inflammatory response caused by hyperglycaemia. In addition, DN inhibits hyperglycaemia-induced activation of oxidative stress by suppressing the expression of p66Shc proteins. Conclusions DZ could efficiently suppress oxidative stress and inflammatory responses to postpone the development of DN, and its mechanism might be related to inhibition of NLRP3 and p66Shc activities. Thus, DZ could be developed into a new therapeutic agent for DN.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::8862fb7e0df9696369811a3a72ce377f
https://doi.org/10.1093/jpp/rgab053 -
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المؤلفون: William Worodria, Richard Kwizera, Felix Bongomin, Freddie Bwanga, Robin Gore, Ronald Olum, Stephen J. Fowler, Bruce Kirenga, David B. Meya, David W. Denning
المصدر: Medical Mycology. 59:923-933
مصطلحات موضوعية: Adult, Male, 0301 basic medicine, medicine.medical_specialty, 030106 microbiology, medicine.disease_cause, 03 medical and health sciences, 0302 clinical medicine, Allergen, Internal medicine, Prevalence, medicine, Palpitations, Aspergillosis, Humans, Uganda, Antibodies, Fungal, Sensitization, Depression (differential diagnoses), Asthma, Lung Diseases, Fungal, business.industry, General Medicine, Odds ratio, Immunoglobulin E, Middle Aged, medicine.disease, respiratory tract diseases, Cross-Sectional Studies, Infectious Diseases, medicine.anatomical_structure, 030228 respiratory system, Population study, Female, Allergic bronchopulmonary aspergillosis, medicine.symptom, business
الوصف: Fungal sensitization is associated with poor asthma control. We aimed to determine the prevalence and factors associated with fungal asthma among Ugandan adults. Individuals aged ≥18 years with a new diagnosis of asthma in the last 12 months participating in the African Severe Asthma Program constituted the study population. Skin prick test results, clinical and demographic data were retrieved from the database, and serum Aspergillus fumigatus specific antibodies and total IgE were measured in stored blood. We enrolled 374 patients, median (IQR) age 34 (25–45) years, 286 (76.5%) females and 286 (76.5%) with severe asthma. Prevalence of Aspergillus fumigatus sensitization was 42.0% (95% CI: 37.1–47.0%), allergic bronchopulmonary aspergillosis (ABPA) 3.2% (1.8–5.5%), severe asthma with fungal sensitization (SAFS) 16% (12.7–20.1%) and allergic bronchopulmonary mycosis (ABPM) 2.9% (1.7–5.2%). Older age (55–64 years) (crude odds ratio (cOR) = 2.6), sensitization to at least one allergen (cOR = 9.38) and hypertension (cOR = 1.99) were significantly associated with Aspergillus sensitization, whereas tertiary education level (cOR = 0.29), severe depression (cOR = 0.15) and strong emotions (cOR = 0.47) were not. High occupational exposure to Aspergillus (cOR = 4.26) and contact with moulds (cOR = 14.28) were significantly associated with ABPA. Palpitations (cOR = 5.54), uncontrolled asthma (cOR = 3.54), eczema/dermatitis (cOR = 3.07), poor lung function (cOR = 2.11) and frequent exacerbations (cOR = 1.01) were significantly associated with SAFS. Eczema/dermatitis (cOR = 1.55) was significantly associated with ABPM, but cold weather trigger (cOR = 0.24) was not. Fungal asthma is a significant problem among Ugandans with asthma and should be particularly considered in individuals who remain uncontrolled despite optimal standard of care for asthma, as it is responsive to available and affordable oral antifungal therapy. Lay Summary This study showed that fungal asthma is a significant problem among Ugandans with asthma with a high prevalence. Fungal asthma should be considered in patients with uncontrolled asthma despite receiving optimal standard of care. This is the first modern attempt to define these endotypes of asthma in Africa.
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المؤلفون: Sho Shibata, Hajime Karasuyama, Soichiro Yoshikawa, Kensuke Miyake
المصدر: International Immunology. 33:809-813
مصطلحات موضوعية: Allergy, Protective immunity, Immunology, hemic and immune systems, chemical and pharmacologic phenomena, General Medicine, Biology, Basophil, medicine.disease_cause, Acquired immune system, medicine.disease, Basophils, Autoimmunity, medicine.anatomical_structure, Immune system, parasitic diseases, medicine, biology.protein, Animals, Humans, Immunology and Allergy, Antibody, Interleukin 4
الوصف: Basophils, the rarest granulocytes, were identified by Paul Ehrlich more than 140 years ago, much earlier than the discovery of T and B cells. Unfortunately, basophils were often mixed up with tissue-resident mast cells because of some phenotypic similarities between them and considered erroneously as minor relatives or blood-circulating precursors of mast cells. Moreover, basophil research was hindered by the rarity of basophils and the paucity of useful analytical tools, and therefore basophils had often been neglected in immunological studies. A series of studies using newly developed tools, including basophil-depleting antibodies and genetically engineered mice deficient only in basophils, have clearly defined previously unrecognized roles of basophils, that are distinct from those played by tissue-resident mast cells. In this mini-review, we highlight recent advances in our understanding of basophil functions, particularly focusing on their roles in the regulation of innate and acquired immunity, allergic reactions, autoimmunity and protective immunity against parasitic infections, mainly based on animal studies. Further studies on human basophils would facilitate the development of new strategies for the treatment of basophil-associated disorders.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::97ff56219907d0a7c04273541c21f802
https://doi.org/10.1093/intimm/dxab021 -
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المؤلفون: M Alzaid, Firas Al-Niaimi, A Al-Naseem, Faisal R. Ali
المصدر: Alzaid, M, Al-Naseem, A, Al-Niaimi, F & Ali, F R 2022, ' Topical timolol in dermatology : infantile haemangiomas and beyond ', Clinical and Experimental Dermatology, vol. 47, no. 5, pp. 819-832 . https://doi.org/10.1111/ced.15021
مصطلحات موضوعية: Male, Chronic wound, medicine.medical_specialty, Angiogenesis, Administration, Topical, Adrenergic beta-Antagonists, Timolol, Dermatology, Scrotum, medicine, Humans, Hemangioma, Capillary, Granuloma, Pyogenic, Keratinocyte migration, Acne, integumentary system, business.industry, medicine.disease, eye diseases, medicine.anatomical_structure, Rosacea, sense organs, medicine.symptom, business, Wound healing, medicine.drug
الوصف: Timolol, a non-selective β-adrenergic receptor blocker, is well-tolerated and is becoming increasingly popular in dermatology especially after its use in the management of infantile hemangiomas. Its effects are mainly due to vasoconstriction, inhibition of angiogenesis and keratinocyte migration promotion for re-epithelialization and wound healing. We review the evidence behind the use of timolol in several dermatological conditions including infantile hemangiomas, pyogenic granulomas, Kaposi's sarcoma, chronic wound healing, post-surgical wounds, acne vulgaris, rosacea, eczema and red scrotum syndrome.
وصف الملف: application/pdf
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المؤلفون: David T. Yeung, Jill A. Harvilchuck, Gennady E. Platoff, Christina M. Wilhelm, Phillip H Beske
المصدر: Mil Med
مصطلحات موضوعية: Male, 0301 basic medicine, medicine.medical_specialty, Physiology, Rodentia, Neutropenia, Feature Article and Original Research, Rats, Sprague-Dawley, Blood cell, 03 medical and health sciences, Lethargy, 0302 clinical medicine, Immune system, Internal medicine, Mustard Gas, medicine, Animals, Humans, Chemical Warfare Agents, Hematology, Respiratory distress, Public Health, Environmental and Occupational Health, General Medicine, medicine.disease, Rats, 030104 developmental biology, medicine.anatomical_structure, Medical Countermeasures, Toxicity, 030221 ophthalmology & optometry, Female, Bone marrow
الوصف: Introduction While exposure to sulfur mustard (SM) is commonly associated with the production of vesicating dermal, ocular, and respiratory injuries, systemic damage to bone marrow and lymphatic tissue can decrease critical immune cell populations leading to higher susceptibility to life-threatening infection and septicemia. There are currently no approved medical countermeasures for SM-induced myelosuppression. An intravenous SM challenge model was developed in adult rats as a preliminary proof-of-principle platform to evaluate the efficacy of candidate immunostimulants. Materials and Methods Adult male and female Sprague Dawley rats were exposed to SM through tail vein injection. Toxicity progression was monitored through clinical observations, body weights, body temperatures, hematology, serum clinical chemistry, and flow cytometry of blood and bone marrow samples. Results Following SM exposure, overt toxicity progression was characterized by weight loss, changes in body temperature, and manifestation of toxic clinical signs (diarrhea, lethargy, hunched posture, rough hair coat, respiratory distress, and death). Drastic alterations in complete blood cell profiles included an early-onset lymphopenia followed by a delayed-onset neutropenia and thrombocytopenia. Only transient changes in serum clinical chemistry parameters were observed. Flow cytometry analysis of circulating blood revealed that B-cells were more predominantly affected by SM exposure than T-cells. Challenge with SM resulted in loss of hematopoietic and mesenchymal stem cell populations in the bone marrow. Conclusions The small animal model developed in this study replicates many key aspects of human SM exposures and should serve as a relevant, rapid, and cost-effective platform to screen candidate medical countermeasures for SM-induced hematologic toxicity.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3bb159ae9de75d53bf768aee44a651e5
https://doi.org/10.1093/milmed/usaa510 -
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المؤلفون: Rohan Morenas, Joseph Kim, Omer A. Raheem, Robert Drury
المصدر: Sexual Medicine Reviews. 10:99-107
مصطلحات موضوعية: Male, medicine.medical_specialty, Urology, Endocrinology, Diabetes and Metabolism, medicine.medical_treatment, Penile Induration, Priapism, Erectile tissue, Penile Implantation, Endocrinology, Fibrosis, Diabetes mellitus, medicine, Humans, Ultrasonography, business.industry, Vascular disease, Prostatectomy, Obstetrics and Gynecology, medicine.disease, Psychiatry and Mental health, medicine.anatomical_structure, Erectile dysfunction, Reproductive Medicine, Etiology, Penile Prosthesis, business
الوصف: Introduction Penile corporal fibrosis may occur secondary to explantation of an infected penile prosthesis, severe penile trauma, refractory low-flow priapism, Peyronie's disease, or chronic intra-cavernous injection of vasoactive drugs. Other etiologies of corporal fibrosis, presenting primarily with erectile dysfunction, can develop in chronic smokers, hypertensive patients, alcoholics, diabetics, and after radical prostatectomy. Corporal erectile tissue fibrosis is a significant pathophysiologic component of erectile dysfunction; however, current ultrasound-based penile imaging protocols do not directly assess it. Objective To determine if grayscale ultrasonography (US) is a suitable imaging modality to identify and assess penile corporal erectile tissue fibrosis. Methods A PubMed literature review was performed for studies that detailed ultrasonographic methods and findings of pathologies causing penile corporal fibrosis. Our main outcome measure was the ultrasonographic findings of pathologies causing penile corporal fibrosis. Results Grayscale US demonstrates the capability to detect and localize the fibrotic changes of the corpora cavernosa. Ultrasonographic findings capture penile corporal tissue heterogeneity including diffuse, circumscribed, or localized patterns. Conclusion Overall, grayscale US may be a useful and convenient imaging modality to assess penile corporal fibrosis secondary to explantation of an infected penile prosthesis, priapism, penile trauma, chronic intra-cavernous injection of vasoactive drugs, diabetes, Peyronie's disease, and vascular disease. While limited by the skill and knowledge of the US operator, the combined knowledge of pathophysiology and US may help clinicians identify and manage the underlying etiology of penile corporal fibrosis. Kim J, Drury R, Morenas R et al. Pathophysiology and Grayscale Ultrasonography of Penile Corporal Fibrosis. Sex Med Rev 2021;XX:XXX–XXX.
URL الوصول: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0741a1618aef3924b4244aad643b95ed
https://doi.org/10.1016/j.sxmr.2021.07.005
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