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The Efficacy of Posttreatment with Synthetic C-Reactive Protein in Murine Bacterial Peritonitis via Activation of FcγRI-Expressing Kupffer Cells.

J Innate Immun 2021 May 4:1-13. Epub 2021 May 4.

Department of Immunology and Microbiology, National Defense Medical College, Tokorozawa, Saitama, Japan.

Pretreatment with synthetic C-reactive protein (CRP), a functional CRP peptide, has the potential to augment macrophage phagocytosis by bacterial challenge. However, the posttreatment is clinically ideal. We investigated the efficacy of posttreatment with synthetic CRP on murine cecal ligation and puncture (CLP), focusing on liver macrophages. Read More

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Pterostilbene nanoparticles with small particle size show excellent anti-breast cancer activity in vitro and in vivo.

Nanotechnology 2021 May 4. Epub 2021 May 4.

Chinese Academy of Medical Sciences and Peking Union Medical College Institute of Medicinal Plant Development, Beijing, CHINA.

Pterostilbene (PTE) is known as resveratrol of the next generation and it has attracted extensive attention in recent years. PTE can inhibit the growth of a variety of tumor cells. To overcome the problem of insolubility, PTE was loaded into nanoparticles (NPs) by anti-solvent precipitation technique using soybean lecithin (SPC) and D-α-tocopheryl polyethylene glycol succinate (TPGS) as stabilizers. Read More

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Untargeted metabolomics for uncovering plasma biological markers of wet age-related macular degeneration.

Aging (Albany NY) 2021 May 4;13. Epub 2021 May 4.

The Key Laboratory for Human Disease Gene Study of Sichuan Province and the Center of Laboratory Medicine, Sichuan Provincial People’s Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan, China.

Wet age-related macular degeneration (wAMD) causes central vision loss and represents a major health problem in elderly people. Here we have used untargeted metabolomics using UHPLC-MS to profile plasma from 127 patients with wAMD (67 choroidal neovascularization (CNV) and 60 polypoidal choroidal vasculopathy (PCV)) and 50 controls. A total of 545 biochemicals were detected. Read More

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Identification of an immune subtype predicting survival risk and immune activity in hepatocellular carcinoma.

Aging (Albany NY) 2021 May 3;13. Epub 2021 May 3.

Toxicology and Functional Laboratory, Shandong Center for Disease Control and Prevention, Jinan 250014, Shandong, China.

Immune checkpoint inhibitors (ICI) prolong the survival for advanced/metastatic patients with lung cancer or melanoma; however, for hepatocellular carcinoma (HCC) patients, a durable response has not been reported. Herein, we used a total of 719 HCC patients with public genomic data to determine potential prognostic and immunogenic subtypes. The non-negative matrix factorization (NMF) method was applied to identify the immune classes and potential subtypes. Read More

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Design, synthesis and biological evaluation of novel benzofuran derivatives as potent LSD1 inhibitors.

Eur J Med Chem 2021 Apr 24;220:113501. Epub 2021 Apr 24.

Key Laboratory of Structure-Based Drug Design & Discovery, Ministry of Education, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.

Lysine-specific demethylase 1 (LSD1) is a FAD-dependent enzyme, which has been proposed as a promising target for therapeutic cancer. Herein, a series of benzofuran derivatives were designed, synthesized and biochemical evaluated as novel LSD1 inhibitors based on scaffold hopping and conformational restriction strategy. Most of the compounds potently suppressed the enzymatic activities of LSD1 and potently inhibited tumor cells proliferation. Read More

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Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma.

Eur J Med Chem 2021 Apr 20;221:113481. Epub 2021 Apr 20.

Department of Cancer Biology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02115, USA; Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, MA, 02115, USA. Electronic address:

Development of inhibitors targeting CDK12/13 is of increasing interest as a potential therapy for cancers as these compounds inhibit transcription of DNA damage response (DDR) genes. We previously described THZ531, a covalent inhibitor with selectivity for CDK12/13. In order to elucidate structure-activity relationship (SAR), we have undertaken a medicinal chemistry campaign and established a focused library of THZ531 analogs. Read More

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Aloperine improves osteoporosis in ovariectomized mice by inhibiting RANKL-induced NF-κB, ERK and JNK approaches.

Int Immunopharmacol 2021 May 1;97:107720. Epub 2021 May 1.

Department of Spinal Surgery, the First Affiliated Hospital, University of South China, Hengyang, Hunan 421000, China. Electronic address:

Presently, postmenopausal osteoporosis mainly caused by excessive activation of in vivo osteoclasts has become a global public health burden. Natural compounds have gradually become the potential drugs for the treatment of postmenopausal osteoporosis. Aloperine is a new alkaloid extracted from the leaves and seeds of sophora bean. Read More

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Internalization of polystyrene microplastics in Euglena gracilis and its effects on the protozoan photosynthesis and motility.

Aquat Toxicol 2021 Apr 18;236:105840. Epub 2021 Apr 18.

College of Biological, Chemical Science and Engineering, Jiaxing University, Jiaxing 314001, P.R. China.

In this study, effects of polystyrene microplastics (MPS) on Euglena gracilis were investigated via examination on its photosynthesis and motility, two typical properties of the protozoan. No adverse effects were observed after 4-d exposure except for decrease in motility at two high MPS concentrations (5 and 25 mg/L). After 8-d duration, MPS at 1 mg/L had no obvious effects on E. Read More

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Aconitine induces mitochondrial energy metabolism dysfunction through inhibition of AMPK signaling and interference with mitochondrial dynamics in SH-SY5Y cells.

Toxicol Lett 2021 May 1. Epub 2021 May 1.

School of Pharmacy and School of Public Health, Chengdu University of Traditional Chinese Medicine, Chengdu, 611137, China. Electronic address:

Aconitine, a highly toxic alkaloid derived from Aconitum L., affects the central nervous system and peripheral nervous system. However, the underlying mechanism of aconitine-induced neurotoxicity remains unclear. Read More

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Circ_ZFP644 attenuates caerulein-induced inflammatory injury in rat pancreatic acinar cells by modulating miR-106b/Pias3 axis.

Exp Mol Pathol 2021 May 1:104644. Epub 2021 May 1.

Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong First Medical University, Jinan, Shandong, China. Electronic address:

(AP) is a kind of inflammatory misorder existing in pancreas. Non-coding RNAs (ncRNAs) have been reported to play important roles in development of AP. The current study was designed to explore the role of circular RNA zinc finger protein 644 (circRNA circ_ZFP644) in caerulein-induced AR42J cells. Read More

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Synthesis of 16β-derivatives of 3-(2-bromoethyl)-estra-1,3,5(10)-trien-17β-ol as inhibitors of 17β-HSD1 and/or steroid sulfatase for the treatment of estrogen-dependent diseases.

Steroids 2021 May 1:108856. Epub 2021 May 1.

Laboratory of Medicinal Chemistry, Endocrinology and Nephrology Unit, CHU de Québec - Research Center (CHUL, T4), Québec, QC, G1V4G2, Canada; Department of Molecular Medicine, Faculty of Medicine, Université Laval, Québec, QC, G1V0A6, Canada. Electronic address:

17β-Hydroxysteroid dehydrogenase type 1 (17β-HSD1) and steroid sulfatase (STS) are involved in the synthesis of the most potent estrogen in the human body, estradiol (E2). These enzymes are known to play a pivotal role in the progression of estrogen-dependent diseases, such as breast cancer and endometriosis. Therefore, the inhibition of 17β-HSD1 and/or STS represents a promising avenue to modulate the growth of estrogen-dependent tumors or lesions. Read More

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Exercise Reduces Pain and Deleterious Histological Effects in Fibromyalgia-like Model.

Neuroscience 2021 May 1. Epub 2021 May 1.

Laboratory of Autoimmunity and Immunopharmacology (LAIF), Department of Health Sciences, Campus Araranguá, Universidade Federal de Santa Catarina, 88906-072 Araranguá, Brazil; Post-Graduate Program of Neuroscience, Center of Biological Science, Campus Florianópolis, Universidade Federal de Santa Catarina, 88040-900 Florianópolis, Brazil. Electronic address:

Fibromyalgia (FM) is characterized by chronic pain and associated comorbidities such as fatigue, anxiety, depression, and sleep disorders. There is a large amount of evidence regarding the benefits of physical exercise in controlling chronic pain. However, there is no consensus on which exercise modality is most suitable and the real benefits of this intervention to treat FM symptoms. Read More

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Novel Lignin-Capped Silver Nanoparticles against Multidrug-Resistant Bacteria.

ACS Appl Mater Interfaces 2021 May 4. Epub 2021 May 4.

Faculty of Medicine, Division of Infectious Diseases, University of British Columbia, Vancouver, British Columbia V6T 1Z4, Canada.

The emergence of bacteria resistant to antibiotics and the resulting infections are increasingly becoming a public health issue. Multidrug-resistant (MDR) bacteria are responsible for infections leading to increased morbidity and mortality in hospitals, prolonged time of hospitalization, and additional burden to financial costs. Therefore, there is an urgent need for novel antibacterial agents that will both treat MDR infections and outsmart the bacterial evolutionary mechanisms, preventing further resistance development. Read More

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Protective role of resolvin D1, a pro-resolving lipid mediator, in nonsteroidal anti-inflammatory drug-induced small intestinal damage.

PLoS One 2021 4;16(5):e0250862. Epub 2021 May 4.

Department of Gastroenterology, Osaka City University Graduate School of Medicine, Osaka, Japan.

Resolvin D1, a specialized pro-resolving lipid mediator produced from docosahexaenoic acid by 15- and 5-lipoxygenase, exerts anti-inflammatory effects driving to the resolution of inflammation. The present study aimed to elucidate its role in small intestinal damage induced by nonsteroidal anti-inflammatory drug (NSAID). Indomethacin was administered orally to C57BL/6J male mice, which were sacrificed 24 h later to collect small intestine specimens. Read More

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C2orf69 mutations disrupt mitochondrial function and cause a multisystem human disorder with recurring autoinflammation.

J Clin Invest 2021 May 4. Epub 2021 May 4.

Department of Pediatrics, RWTH Aachen University, Aachen, Germany.

Background: Deciphering the function of the many genes previously classified as uncharacterized "open reading frame" (orf) completes our understanding of cell function and its pathophysiology.

Methods: Whole-exome sequencing, yeast 2-hybrid and transcriptome analyses together with molecular characterization are used here to uncover the function of the C2orf69 gene.

Results: We identified loss-of-function mutations in the uncharacterized C2orf69 gene in eight individuals with brain abnormalities involving hypomyelination and microcephaly, liver dysfunction and recurrent autoinflammation. Read More

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Pseudomonas aeruginosa induces spatio-temporal secretion of IL-1β, TNFα, proMMP-9, and reduction of epithelial E-cadherin in human alveolar epithelial type II (A549) cells.

Acta Biochim Pol 2021 May 4. Epub 2021 May 4.

Department of Inmunobioquímica, Instituto Nacional de Perinatología "Isidro Espinoza de los Reyes" (INPerIER), Ciudad de México, México.

Pseudomonas aeruginosa, is an opportunistic bacterium with a high prevalence in diverse pulmonary infections. Although several genes are involved in the system of resistance and evasion of the immunological response of the host, little is known about the inflammatory, degradative, and cell-binding response induced by P. aeruginosa in human lung alveolar epithelial cells. Read More

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Photobiomodulation of mineralisation in mesenchymal stem cells.

Photochem Photobiol Sci 2021 May 4. Epub 2021 May 4.

Department of Oral Sciences, Faculty of Dentistry, Sir John Walsh Research Institute, University of Otago, PO Box 56, Dunedin, 9054, New Zealand.

Mesenchymal stem cells (MSCs) and photobiomodulation (PBM) both offer significant therapeutic potential in regenerative medicine. MSCs have the ability to self-renew and differentiate; giving rise to multiple cellular and tissue lineages that are utilised in repair and regeneration of damaged tissues. PBM utilises light energy delivered at a range of wavelengths to promote wound healing. Read More

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Development and interpretation of a QSAR model for in vitro breast cancer (MCF-7) cytotoxicity of 2-phenylacrylonitriles.

J Comput Aided Mol Des 2021 May 4. Epub 2021 May 4.

Department of Chemistry, Tschannen Science Center, California State University at Sacramento, 6000 J Street, Sacramento, CA, 95819, USA.

The Arylhydrocarbon Receptor (AhR), a member of the Per-ARNT-SIM transcription factor family, has been as a potential new target to treat breast cancer sufferers. A series of 2-phenylacrylonitriles targeting AhR has been developed that have shown promising and selective activity against cancerous cell lines while sparing normal non-cancerous cells. A quantitative structure-activity relationship (QSAR) modeling approach was pursued in order to generate a predictive model for cytotoxicity to support ongoing synthetic activities and provide important structure-activity information for new structure design. Read More

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Apoptosis-mediated anticancer activity in prostate cancer cells of a chestnut honey (Castanea sativa L.) quinoline-pyrrolidine gamma-lactam alkaloid.

Amino Acids 2021 May 4. Epub 2021 May 4.

Department of Pharmacological and Biomolecular Sciences, University of Milan, 20133, Milan, Italy.

Prostate cancer (PCa) is the most common malignancy in men and represents the second leading cause of cancer deaths in Western countries. PCa is initially androgen-dependent, however, this tumor inevitably progresses as castration-resistant prostate cancer (CRPC), which represents the most aggressive phase of the pathology. In this work, in two CRPC cell lines (DU145 and PC3), we studied the in vitro inhibitory properties of the tryptophan-derived endogenous metabolite kynurenic acid (KYNA) and of the lactam form of 3-2'-pyrrilonidinyl-kynurenic acid (3-PKA-L), alkaloids usually present in combination in chestnut honey. Read More

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Okur-Chung neurodevelopmental syndrome-linked CK2α variants have reduced kinase activity.

Hum Genet 2021 May 4. Epub 2021 May 4.

Institut de Psychiatrie et Neurosciences de Paris (IPNP), UMR S1266, INSERM, Université de Paris, Paris, France.

The Okur-Chung neurodevelopmental syndrome, or OCNDS, is a newly discovered rare neurodevelopmental disorder. It is characterized by developmental delay, intellectual disability, behavioral problems (hyperactivity, repetitive movements and social interaction deficits), hypotonia, epilepsy and language/verbalization deficits. OCNDS is linked to de novo mutations in CSNK2A1, that lead to missense or deletion/truncating variants in the encoded protein, the protein kinase CK2α. Read More

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Human hydatid cyst fluid-induced therapeutic anti-cancer immune responses via NK1.1 cell activation in mice.

Cancer Immunol Immunother 2021 May 4. Epub 2021 May 4.

Laboratorio de Glicobiología e Inmunología Tumoral, Institut Pasteur de Montevideo, 11400, Montevideo, CP, Uruguay.

Echinococcus granulosus is a cestode parasite which causes cystic echinococcosis disease. Previously we observed that vaccination with E. granulosus antigens from human hydatid cyst fluid (HCF) significantly inhibits colon cancer growth. Read More

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Permeant fluorescent probes visualize the activation of SARM1 and uncover an anti-neurodegenerative drug candidate.

Elife 2021 May 4;10. Epub 2021 May 4.

School of Life and Health Sciences, The Chinese University of Hong Kong (Shenzhen), Shenzhen, China.

SARM1 regulates axonal degeneration through its NAD-metabolizing activity and is a drug target for neurodegenerative disorders. We designed and synthesized fluorescent conjugates of styryl derivative with pyridine to serve as substrates of SARM1, which exhibited large red-shifts after conversion. With the conjugates, SARM1 activation was visualized in live cells following elevation of endogenous NMN or treatment with a cell-permeant NMN-analog. Read More

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Photocross-Linked Antimicrobial Amino-Siloxane Elastomers.

ACS Appl Mater Interfaces 2021 May 4. Epub 2021 May 4.

Department of Chemistry, 2036 Main Mall, University of British Columbia, Vancouver, British Columbia V6T 1Z1, Canada.

Mechanically robust bulk antimicrobial polymers are one way to address disease transmission via contaminated surfaces. Here, we demonstrate the visible light photo-oxidative cross-linking of amine-containing PDMS using a single-component, solvent-free system where amines have a dual role as antimicrobial functionalities and cross-linking sites. Rose Bengal, a xanthene dye used as a fluorescent stain, is thermally reacted with the polymer to give a solvent-free liquid siloxane that can generate reactive singlet oxygen upon aerobic green light irradiation, coupling the amine functionalities into imine cross-links. Read More

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Gold Cluster Capped with a BCL-2 Antagonistic Peptide Exerts Synergistic Antitumor Activity in Chronic Lymphocytic Leukemia Cells.

ACS Appl Mater Interfaces 2021 May 4. Epub 2021 May 4.

Department of Chemistry and Biology, Faculty of Environment and Life Science, Beijing University of Technology, Beijing 100124, China.

Chronic lymphocytic leukemia (CLL) is still incurable by conventional chemotherapy due to the resistance to apoptosis. We have previously found that a peptide-capped gold cluster (AuSv) can target on the aberrant oxidative stress in CLL cells to specially inhibit thioredoxin reductase (TrxR) activity, resulting in significant apoptosis. However, the required doses of the gold cluster for inducing apoptosis are high, restricting its potential for further applications. Read More

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Galectin-1 ameliorates perioperative neurocognitive disorders in aged mice.

CNS Neurosci Ther 2021 May 4. Epub 2021 May 4.

Department of Anesthesiology, Sun Yat-sen Memorial Hospital, Sun Yat-sen University, Guangzhou, China.

Introduction: The incidence of perioperative neurocognitive disorders (PND) is higher in the elderly patients undergoing surgery. Microglia activation-mediated neuroinflammation is one of the hallmarks of PND. Galectin-1 has been identified as a pivotal modulator in the central nervous system (CNS), while the role of galectin-1 in PND induced by microglia-mediated neuroinflammation is still undetermined. Read More

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MiR-664-3p suppresses osteoblast differentiation and impairs bone formation via targeting Smad4 and Osterix.

J Cell Mol Med 2021 May 4. Epub 2021 May 4.

Jiangsu Key Laboratory of Xenotransplantation, Nanjing Medical University, Nanjing, China.

Osteoporosis is a metabolic disorder characterized by low bone mass and deteriorated microarchitecture, with an increased risk of fracture. Some miRNAs have been confirmed as potential modulators of osteoblast differentiation to maintain bone mass. Our miRNA sequencing results showed that miR-664-3p was significantly down-regulated during the osteogenic differentiation of the preosteoblast MC3T3-E1 cells. Read More

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Microglia-mediated phagocytosis of apoptotic nuclei is impaired in the adult murine hippocampus after stroke.

Glia 2021 May 4. Epub 2021 May 4.

Hans-Berger Department of Neurology, Jena University Hospital, Jena, Germany.

Following stroke, neuronal death takes place both in the infarct region and in brain areas distal to the lesion site including the hippocampus. The hippocampus is critically involved in learning and memory processes and continuously generates new neurons. Dysregulation of adult neurogenesis may be associated with cognitive decline after a stroke lesion. Read More

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Exercise training rescues the electrical activity of liver-projecting DMNV neurones in response to oxytocin in spontaneously hypertensive rats.

J Neuroendocrinol 2021 May 4:e12977. Epub 2021 May 4.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil.

A neural circuit between the paraventricular nucleus of the hypothalamus (PVN) and the dorsal motor nucleus of the vagus (DMNV) constitutes part of an important parasympathetic autonomic pathway that controls hepatic glucose production. Intracerebroventricular injection of insulin activates oxytocinergic neurones in the PVN and elicits the release of oxytocin into the circulation, which plays an important role in the metabolism of glucose. Moreover, the central action of insulin can reduce the concentration of glucose in blood taken from the hepatic vein of Wistar rats via activation of vagal efferent nerves to the liver. Read More

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Muscarinic M and M receptor subtypes in the ventral subiculum differentially modulate alcohol seeking vs consumption in male alcohol preferring rats.

Br J Pharmacol 2021 May 3. Epub 2021 May 3.

Florey Institute of Neuroscience and Mental Health, Parkville, Australia, 3052.

Background And Purpose: Muscarinic acetylcholine receptors (mAChRs) mediate alcohol consumption and seeking in rats, and while M and M mAChRs have recently been implicated to mediate these behaviours in the striatum, their role in other regions remain unknown. The ventral tegmental area (VTA) and ventral subiculum (vSub) both densely express M and M mAChRs and modulate alcohol seeking via their projections to the nucleus accumbens shell (AcbSh).

Experimental Approach: In Indiana alcohol preferring (iP) male rats we examined Chrm4 (M ) and Chrm5 (M ) expression in the VTA and vSub following long-term alcohol consumption and abstinence using RT-qPCR. Read More

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Proof-of-concept for clinical effects of oral rilzabrutinib, the first Bruton tyrosine kinase inhibitor for pemphigus vulgaris: the phase 2 BELIEVE study.

Br J Dermatol 2021 May 3. Epub 2021 May 3.

Department of Dermatology, Rouen University Hospital, Centre de Référence des Maladies Bulleuses Autoimmunes, and INSERM U1234, Normandie University, Rouen, France.

Background: Bruton tyrosine kinase (BTK) inhibition targets B-cell and other non-T-cell immune cells implicated in pemphigus pathophysiology, an autoimmune disease driven by anti-desmoglein autoantibodies. Rilzabrutinib is a new reversible, covalent BTK inhibitor demonstrating preclinical efficacy as monotherapy in canine pemphigus foliaceus.

Objectives: Evaluate efficacy and safety of oral rilzabrutinib in pemphigus vulgaris patients in a multicenter, proof-of-concept, phase 2 trial. Read More

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