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Out of balance: the role of evolutionary mismatches in the sex disparity in autoimmune disease.

Med Hypotheses 2021 Mar 29;151:110558. Epub 2021 Mar 29.

Department of Anthropology, University College London, UK.

Over the past century autoimmune disease incidence has increased rapidly in (post-) industrialised, affluent societies, suggesting that changes in ecology and lifestyle are driving this development. Epidemiological studies show that (i) 80% of autoimmune disease patients are female, (ii) autoimmune diseases co-occur more often in women, and (iii) the incidence of some autoimmune diseases is increasing faster in women than in men. The female preponderance in autoimmunity is most pronounced between puberty and menopause, suggesting that diverging sex hormone levels during the reproductive years are implicated in autoimmune disease development. Read More

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"We can't just have a casual conversation": An institutional ethnography-informed study of work in labour and birth.

Soc Sci Med 2021 Apr 29;279:113975. Epub 2021 Apr 29.

Wilson Centre for Research in Education, University Health Network, University of Toronto, Canada; University of Toronto's Centre for Interprofessional Education, University Health Network, Canada; Department of Speech-Language Pathology, University of Toronto, Canada.

Labour and delivery units often become contested workplaces with tensions between obstetrics, nursing, and midwifery practices. These tensions can impede communication and raise concerns about provider wellness and patient safety. Remedying such tensions requires inquiry into the drivers of recurrent problems in interprofessional practice. Read More

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Circulating Epstein-Barr virus DNA level post induction chemotherapy contributes to prognostication in advanced-stage nasopharyngeal carcinoma.

Eur J Cancer 2021 May 5;151:63-71. Epub 2021 May 5.

Department of Radiation Oncology, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-Sen University Cancer Center, No. 651 Dongfeng Eastern Road, Guangzhou, 510060, China. Electronic address:

Background: To investigate the value of post-induction chemotherapy (IC) cell-free Epstein-Barr virus DNA (cfEBV DNA) for prognostication in locally advanced nasopharyngeal carcinoma (LA-NPC).

Methods: A total of 910 histologically proven LA-NPC undergoing radical IC + concurrent chemo-radiotherapy (CCRT) or targeted radiotherapy (CTRT) or both (CTCRT) were involved. The concentration of cfEBV DNA was measured by quantitative polymerase chain reaction pre-IC (cfEBV DNA) and at IC completion. Read More

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Arrhythmia incidence and associated factors during volatile induction of general anesthesia with sevoflurane: a retrospective analysis of 950 adult patients.

Anaesth Crit Care Pain Med 2021 May 5:100878. Epub 2021 May 5.

Department of Anaesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea. Electronic address:

Background: Sevoflurane has been used to induce anaesthesia in adults due to its suitability for airway management and haemodynamic stability. Few studies have reported arrhythmia during volatile induction with sevoflurane in adults. Here, we investigated the incidence of arrhythmia and risk factors associated with its occurrence during sevoflurane induction of anaesthesia in adults. Read More

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Plumbagin suppresses non-small cell lung cancer progression through downregulating ARF1 and by elevating CD8 cells.

Pharmacol Res 2021 May 5:105656. Epub 2021 May 5.

Dr. Neher's Biophysics Laboratory for Innovative Drug Discovery, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau (SAR), China; State Key Laboratory of Quality Research in Chinese Medicine, Macau University of Science and Technology, Avenida Wai Long, Taipa, Macau (SAR), China; Guangdong-Hong Kong-Macau Joint Lab on Chinese Medicine and Immune Disease Research. Electronic address:

Non-small cell lung cancer (NSCLC) is one of the most frequently diagnosed cancers and the leading causes of cancer death worldwide. Therefore, new therapeutic agents are urgently needed to improve patient outcomes. Plumbagin (PLB), a natural sesquiterpene present in many Chinese herbal medicines, has been reported for its anti-cancer activity in various cancer cells. Read More

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Microbiome analysis reveals gut microbiota alteration in mice with the effect of matrine.

Microb Pathog 2021 May 5:104926. Epub 2021 May 5.

College of Animal Science and VeterinaryMedicine, Xinyang Agriculture And Forestry University, Xinyang, China.

Mounting evidence revealed the negative effects of abuse of antibiotic including the induction of decreased immunity and dysbacteriosis. Matrine displayed multiple beneficial effects such as anti-inflammatory, antiviral and antibacterial, but studies of its influence on gut microbiota are still insufficient to report. Here, the present study was conducted to investigate the influence of matrine on the gut microbiota of mice and amoxicillin was used as a positive control. Read More

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Effect of gamma rays and colchicine on silymarin production in cell suspension cultures of Silybum marianum: a transcriptomic study of key genes involved in the biosynthetic pathway.

Gene 2021 May 5:145700. Epub 2021 May 5.

Department of Biology, Health, and Environment, Faculty of Pharmacy, University of Barcelona, Barcelona, Spain.

The aim of this study was to investigate secondary metabolite production in Silybum marianum L. cell suspension cultures obtained from seeds treated with gamma rays (200 and 600Gy) and 0.05% colchicine. Read More

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A Literature Overview on Epilepsy and Inflammasome Activation.

Brain Res Bull 2021 May 5. Epub 2021 May 5.

CNR Neuroscience Institute, Milan, Italy.

Epilepsy is one of the most prevalent serious brain disorders worldwide. Accumulating evidence has suggested that inflammation participates in the progression and pathogenesis of epilepsy. During inflammation, a cytosolic multimolecular complex called the "inflammasome" is activated, driving the innate immune response. Read More

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Hierarchical mesoporous zinc-imidazole dicarboxylic acid MOFs: Surfactant-directed synthesis, pH-responsive degradation, and drug delivery.

Int J Pharm 2021 May 5:120685. Epub 2021 May 5.

Department of pharmaceutical nanotechnology, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz-Iran; Center for Nanotechnology in Drug Delivery, School of Pharmacy, Shiraz University of Medical Sciences, Shiraz-Iran. Electronic address:

The surfactant template-directed solvothermal method was applied in the synthesis of hierarchical mesoporous zinc-imidazolate derivative metal-organic framework (mesoMOF), which was then utilized for active loading of cisplatin (cis-Pt). To fabricate mesoMOF, various amounts of the surfactant (cetyltrimethylammonium bromide: 0.1- 0. Read More

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Nasal vaccination against SARS-CoV-2: synergistic or alternative to intramuscular vaccines?

Int J Pharm 2021 May 5:120686. Epub 2021 May 5.

IDentity, 19 Cavendish Crescent North, The Park, Nottingham, NG71BA, United Kingdom. Electronic address:

It is striking that all marketed SARS-CoV-2 vaccines are developed for intramuscular administration designed to produce humoral and cell mediated immune responses, preventing viremia and the COVID-19 syndrome. They have a high degree of efficacy in humans (70-95%) depending on the type of vaccine. However, little protection is provided against viral replication and shedding in the upper airways due to the lack of a local sIgA immune response, indicating a risk of transmission of virus from vaccinated individuals. Read More

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Trichinella spiralis excretory-secretory products downregulate MMP-9 in Dark Agouti rats affected by experimental autoimmune encephalomyelitis.

Exp Parasitol 2021 May 5:108112. Epub 2021 May 5.

Institute for the Application of Nuclear Energy INEP, University of Belgrade, Banatska 31b, 11080, Belgrade, Serbia.

Matrix metalloproteinases (MMPs), are implicated in the pathogenesis of multiple sclerosis (MS) and in its animal model, experimental autoimmune encephalomyelitis (EAE). Our aim was to investigate whether amelioration of EAE in Dark Agouti (DA) rats, induced by Trichinella spiralis muscle larvae excretory-secretory products (ES L1), could be related to the level and activity of gelatinases, MMP-9 and MMP-2. Serum levels of MMP-9, MMP-2, NGAL/MMP-9, TIMP-1, and cytokines, evaluated by gel-zymography or ELISA, as well as gelatinases and TIMP-1 expression in the spinal cord (SC), were determined in: i) EAE induced, ii) ES L1-treated EAE induced animals. Read More

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Ergothioneine mitigates cisplatin-evoked nephrotoxicity via targeting Nrf2, NF-κB, and apoptotic signaling and inhibiting γ-glutamyl transpeptidase.

Life Sci 2021 May 5:119572. Epub 2021 May 5.

Department of Biochemistry, Faculty of Pharmacy, Al-Azhar University, Cairo 11751, Egypt.

Aim: Cisplatin is a potent chemotherapeutic agent whose therapeutic application is hindered by the associated nephrotoxicity. Cisplatin-evoked nephrotoxicity has been largely attributed to the induction of oxidative stress and inflammatory responses. The current study aimed at investigating the ability of ergothioneine to mitigate cisplatin-evoked nephrotoxicity and to elucidate the underlining molecular mechanisms. Read More

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Sequence For Surgical Resection of Primary Lung Tumor For Oligometastatic Non-Small Cell Lung Cancer.

Ann Thorac Surg 2021 May 5. Epub 2021 May 5.

Division of Thoracic Oncology, Department of Chest Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.

Background: Differing surgical series for the treatment of primary lung tumor with synchronous oligometastatic stage IV non-small cell lung cancer (NSCLC) have been published; however, outcomes remain ambiguous.

Methods: Patients with synchronous oligometastatic stage IV NSCLC treated from 2005 to 2017 were enrolled to identify the impact of treatment sequence (primary lung resection versus systemic treatment) on progression-free survival (PFS) and overall survival (OS).

Results: Fifty-one patients received tumor resection (84% adenocarcinoma, 55% non-smokers, and 65% driver gene mutation). Read More

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Loss of Cxcr4 in Endometriosis Reduces Proliferation and Lesion Number while Increasing Intraepithelial Lymphocyte Infiltration.

Am J Pathol 2021 May 5. Epub 2021 May 5.

Department of Obstetrics, Gynecology, & Reproductive Medicine, Yale School of Medicine, New Haven, CT, USA.

Hyperactivation of the CXCL12-CXCR4 axis occurs in endometriosis; the therapeutic potential of treatments aimed at global inhibition of the axis was recently demonstrated. As CXCR4 is predominantly expressed on epithelial cells in the uterus, our aim was to explore the effects of targeted disruption of CXCR4 in endometriosis lesions. Uteri derived from adult female mice homozygous for a floxed allele of CXCR4 and co-expressing Cre recombinase under control of progesterone receptor were sutured onto the peritoneum of cycling GFP+ host mice. Read More

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Retinoic acid stimulates transcription of the rat SHARP-2 gene via multiple pathways.

J Biochem 2021 May 8. Epub 2021 May 8.

Matsumoto University Graduate School of Health Science, 2095-1 Niimura, Matsumoto, Nagano 390-1295, Japan.

Members of the enhancer of split- and hairy-related protein (SHARP) family, SHARP-1 and SHARP-2, are basic helix-loop-helix transcriptional repressors and belong to the clock genes. In this study, an effect of retinoic acid (RA) on the SHARP family gene expression in the differentiated cells was examined. RA rapidly and temporarily induced the SHARP-2 mRNA expression in hepatic H4IIE cells. Read More

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Tetramethylpyrazine supplementation improves performance, digestion, blood and immune state of broilers exposure to oxidative stress.

J Anim Physiol Anim Nutr (Berl) 2021 May 8. Epub 2021 May 8.

Department of Animal Science, Henan University of Science and Technology, Luoyang, China.

This study aimed to investigate the effect of dietary tetramethylpyrazine (TMP) on the growth performance, nutrient digestion, blood parameters and immunity of broilers under oxidative stress. Five treatments included negative control, positive control with lipopolysaccharide induction and TMP addition at 50, 100 and 150 mg/kg of diet using 600 male Arbor Acres broiler chicks. Results showed that during 1-14 days of age, body weight gain and feed efficiency in the positive control were worsened (p < . Read More

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Hippocampal subfield-specific Homer1a expression is triggered by learning-facilitated long-term potentiation and long-term depression at medial perforant path synapses.

Hippocampus 2021 May 8. Epub 2021 May 8.

Medical Faculty, Department of Neurophysiology, Ruhr University Bochum, Bochum, Germany.

Learning about general aspects, or content details, of space results in differentiated neuronal information encoding within the proximodistal axis of the hippocampus. These processes are tightly linked to long-term potentiation (LTP) and long-term depression (LTD). Here, we explored the precise sites of encoding of synaptic plasticity in the hippocampus that are mediated by information throughput from the perforant path. Read More

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The role of metabolic reprogramming and de novo amino acid synthesis in collagen protein production by myofibroblasts: implications for organ fibrosis and cancer.

Amino Acids 2021 May 8. Epub 2021 May 8.

Department of Medicine, Section of Pulmonary and Critical Care Medicine, The University of Chicago, 5841 S. Maryland Avenue, MC6026, Chicago, IL, 60637, USA.

Fibrosis is a pathologic condition resulting from aberrant wound healing responses that lead to excessive accumulation of extracellular matrix components, distortion of organ architecture, and loss of organ function. Fibrotic disease can affect every organ system; moreover, fibrosis is an important microenvironmental component of many cancers, including pancreatic, cervical, and hepatocellular cancers. Fibrosis is also an independent risk factor for cancer. Read More

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Profile of patients with inflammatory bowel disease in conjunction with unmet needs and decision-making for choosing a new biologic therapy: a baseline analysis of the VEDO-Study.

Int J Colorectal Dis 2021 May 8. Epub 2021 May 8.

Kompetenznetz Darmerkrankungen, Kiel, Germany.

Purpose: We characterized the profile of Crohn's disease (CD) or ulcerative colitis (UC) biologic-naïve patients (starting a new therapy with vedolizumab or TNFα-antagonists), their baseline disease activity predictors, and their perception of the quality of life (HRQoL).

Methods: The VEDO-Study is a real-world study on the effectiveness of vedolizumab vs other biologics as induction and maintenance therapy for CD and UC. A total of 627 CD and 546 UC patients were enrolled from IBD-experienced centers across Germany. Read More

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FACT interacts with Set3 HDAC and fine-tunes GAL1 transcription in response to environmental stimulation.

Nucleic Acids Res 2021 May 8. Epub 2021 May 8.

State Key Laboratory of Protein and Plant Gene Research, School of Life Sciences and Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China.

The histone chaperone facilitates chromatin transactions (FACT) functions in various DNA transactions. How FACT performs these multiple functions remains largely unknown. Here, we found, for the first time, that the N-terminal domain of its Spt16 subunit interacts with the Set3 histone deacetylase complex (Set3C) and that FACT and Set3C function in the same pathway to regulate gene expression in some settings. Read More

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[Effects of dexmedetomidine doses on postoperative cognitive dysfunction and serum β- amyloid and cytokine levels in elderly patients after spine surgery: a randomized controlled trial].

Nan Fang Yi Ke Da Xue Xue Bao 2021 Apr;41(4):600-606

Department of Anesthesiology, First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou 510000, China.

Objective: To explore the immunomodulatory mechanism and optimal dose of dexmedetomidine (DEX) for preventing postoperative cognitive dysfunction (POCD) in elderly patients undergoing spinal surgery.

Objective: A total of 120 elderly patients undergoing elective spinal surgery with general anesthesia were randomized into 4 groups to receive a loading dose of 0.3 μg/kg DEX for 10 min before anesthesia induction followed by maintenance doses of 0. Read More

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3D Printing of Strontium Silicate Microcylinder-Containing Multicellular Biomaterial Inks for Vascularized Skin Regeneration.

Adv Healthc Mater 2021 May 8:e2100523. Epub 2021 May 8.

State Key Laboratory of High Performance Ceramics and Superfine Microstructure, Shanghai Institute of Ceramics, Chinese Academy of Sciences, Shanghai, 200050, P. R. China.

The reconstruction of dermal blood vessels is essential for skin regeneration process. However, the lack of vascular structure, insufficient angiogenesis induction, and ineffective graft-host anastomosis of the existing skin substitutes are major bottle-necks for permanent skin replacement in tissue engineering. In this study, the uniform strontium silicate (SS) microcylinders are successfully synthesized and integrated into the biomaterial ink to serve as stable cell-induced factors for angiogenesis, and then a functional skin substitute based on a vascularization-induced biomimetic multicellular system is prepared via a "cell-writing" bioprinting technology. Read More

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Upregulation of Nogo-B by HIF-1 and AP-1 in hepatocellular carcinoma.

Cancer Sci 2021 May 8. Epub 2021 May 8.

Department of Clinical Laboratory, Shanghai Children's Hospital, Shanghai Jiaotong University, Shanghai, 200062, China.

Nogo-B is an important regulator of tumor angiogenesis. Expression of Nogo-B is remarkably upregulated in multiple tumor types, especially hepatocellular carcinoma (HCC). Here, we show the transcriptional regulation mechanisms of Nogo-B in liver cancer. Read More

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Concomitant use of isavuconazole and CYP3A4/5 inducers: where pharmacogenetics meets pharmacokinetics.

Mycoses 2021 May 8. Epub 2021 May 8.

Department of Pharmaceutical and Pharmacological Sciences, KU Leuven, Pharmacy Department, University Hospitals Leuven, Leuven, Belgium.

Background: Isavuconazole is a triazole antifungal drug, approved for the treatment of invasive aspergillosis and mucormycosis. Isavuconazole is metabolized by CYP3A4 and CYP3A5 and it has been shown that the CYP3A inducer rifampin reduces isavuconazole exposure. By extrapolation, the concomitant use of isavuconazole with moderate and strong CYP450-inducers is contra-indicated, although it is known that some CYP450-inducers are less potent in comparison with rifampin. Read More

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Cold-induction of afadin in brown fat supports its thermogenic capacity.

Sci Rep 2021 May 7;11(1):9794. Epub 2021 May 7.

Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.

The profound energy-expending nature of brown adipose tissue (BAT) thermogenesis makes it an attractive target tissue to combat obesity-associated metabolic disorders. While cold exposure is the strongest inducer of BAT activity, the temporal mechanisms tuning BAT adaptation during this activation process are incompletely understood. Here we show that the scaffold protein Afadin is dynamically regulated by cold in BAT, and participates in cold acclimation. Read More

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A candidate gene identified in converting platycoside E to platycodin D from Platycodon grandiflorus by transcriptome and main metabolites analysis.

Sci Rep 2021 May 7;11(1):9810. Epub 2021 May 7.

School of Pharmacy, Anhui University of Chinese Medicine, Hefei, 230012, China.

Platycodin D and platycoside E are two triterpenoid saponins in Platycodon grandiflorus, differing only by two glycosyl groups structurally. Studies have shown β-Glucosidase from bacteria can convert platycoside E to platycodin D, indicating the potential existence of similar enzymes in P. grandiflorus. Read More

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A chimeric dengue virus vaccine candidate delivered by high density microarray patches protects against infection in mice.

NPJ Vaccines 2021 May 7;6(1):66. Epub 2021 May 7.

Australian Infectious Diseases Research Centre, School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane, QLD, Australia.

Dengue viruses (DENV) cause an estimated 390 million infections globally. With no dengue-specific therapeutic treatment currently available, vaccination is the most promising strategy for its control. A wide range of DENV vaccines are in development, with one having already been licensed, albeit with limited distribution. Read More

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ADIPOR1 deficiency-induced suppression of retinal ELOVL2 and docosahexaenoic acid levels during photoreceptor degeneration and visual loss.

Cell Death Dis 2021 May 7;12(5):458. Epub 2021 May 7.

Laboratory of Retinal Cell Biology, Tokyo, Japan.

Lipid metabolism-related gene mutations can cause retinitis pigmentosa, a currently untreatable blinding disease resulting from progressive neurodegeneration of the retina. Here, we demonstrated the influence of adiponectin receptor 1 (ADIPOR1) deficiency in retinal neurodegeneration using Adipor1 knockout (KO) mice. Adipor1 mRNA was observed to be expressed in photoreceptors, predominately within the photoreceptor inner segment (PIS), and increased after birth during the development of the photoreceptor outer segments (POSs) where photons are received by the visual pigment, rhodopsin. Read More

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Loss of immune homeostasis in patients with idiopathic pulmonary arterial hypertension.

Thorax 2021 May 7. Epub 2021 May 7.

Department of Pulmonary Medicine, Erasmus Universiteit Rotterdam, Rotterdam, The Netherlands

Introduction: Autoreactivity against pulmonary vascular structures is thought to be involved in idiopathic pulmonary arterial hypertension (IPAH), but the underlying mechanisms remain poorly understood. We hypothesised that aberrant B-cell activation contributes to IPAH aetiology.

Methods: Mice with enhanced B-cell activation due to B-cell-specific overexpression of the B-cell receptor (BCR) signalling molecule Bruton's tyrosine kinase (BTK) were subjected to lung injury and examined for several pulmonary hypertension (PH) indices. Read More

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Macrophage miR-210 induction and metabolic reprogramming in response to pathogen interaction boost life-threatening inflammation.

Sci Adv 2021 May 7;7(19). Epub 2021 May 7.

Laboratory of Tumor Inflammation and Angiogenesis, CCB, VIB, Leuven, Belgium.

Unbalanced immune responses to pathogens can be life-threatening although the underlying regulatory mechanisms remain unknown. Here, we show a hypoxia-inducible factor 1α-dependent microRNA (miR)-210 up-regulation in monocytes and macrophages upon pathogen interaction. MiR-210 knockout in the hematopoietic lineage or in monocytes/macrophages mitigated the symptoms of endotoxemia, bacteremia, sepsis, and parasitosis, limiting the cytokine storm, organ damage/dysfunction, pathogen spreading, and lethality. Read More

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