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About 24,013 results

Caspase-4/11 exacerbates disease severity in SARS-CoV-2 infection by promoting inflamma...
https://doi.org/10.1073/pnas.2202012119
Proceedings of the National Academy of Sciences of the Un... Eltobgy MM, Zani A et. al.

May 20th, 2022 - SignificanceWe report the discovery of fundamental roles for the noncanonical inflammasome molecule Caspase-4/11 in promoting pathological inflammatory and prothrombotic pathways in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Our work demonstrates that Caspase-11 has a broader role in immune responses beyond its previously appreciated effects in bacterial infections...

Mast cell infiltration of the choroid and protease release are early events in age-rela...
https://doi.org/10.1073/pnas.2118510119
Proceedings of the National Academy of Sciences of the Un... Mcharg S, Booth L et. al.

May 14th, 2022 - SignificanceGenome-wide association studies have identified two major risk loci for age-related macular degeneration (AMD) on chromosome (Chr) 1 and Chr10. Here, we use proteomics to analyze submacular stromal tissue punches from older eye donors without AMD, comparing tissue from donors who were homozygous for high-risk alleles at Chr1 or Chr10 with tissue from donors with low risk at these tw...

A potential new treatment for CDKL5 deficiency disorder.
https://doi.org/10.1016/S1474-4422(22)00127-2
The Lancet. Neurology; Gill D

Apr 17th, 2022 - A potential new treatment for CDKL5 deficiency disorder.|2022|Gill D,|enzymology,therapy,deficiency,drug therapy,

Safety and efficacy of ganaxolone in patients with CDKL5 deficiency disorder: results f...
https://doi.org/10.1016/S1474-4422(22)00077-1
The Lancet. Neurology; Knight EMP, Amin S et. al.

Apr 17th, 2022 - CDKL5 deficiency disorder (CDD) is a rare, X-linked, developmental and epileptic encephalopathy characterised by severe global developmental impairment and seizures that can begin in the first few months after birth and are often treatment refractory. Ganaxolone, an investigational neuroactive steroid, reduced seizure frequency in an open-label, phase 2 trial that included patients with CDD. We...

RNA N6-methyladenosine demethylase FTO promotes pancreatic cancer progression by induci...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106577
Oncogene Tan Z, Shi S et. al.

Apr 16th, 2022 - RNA N6-methyladenosine (m6A) is an emerging regulator of mRNA modifications and represents a novel player in tumorigenesis. Although it has functional significance in both pathological and physiological processes, the role of m6A modification in pancreatic ductal cancer (PDAC) remains elusive. Here, we showed that high fat mass and obesity-associated gene (FTO) expression was associated with a ...

Structural Basis of the Main Proteases of Coronavirus Bound to Drug Candidate PF-07321332.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044943
Journal of Virology; Li J, Lin C et. al.

Apr 8th, 2022 - The high mutation rate of COVID-19 and the prevalence of multiple variants strongly support the need for pharmacological options to complement vaccine strategies. One region that appears highly conserved among different genera of coronaviruses is the substrate-binding site of the main protease (Mpro or 3CLpro), making it an attractive target for the development of broad-spectrum drugs for multi...

SARS-CoV-2 nsp5 Exhibits Stronger Catalytic Activity and Interferon Antagonism than Its...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9044939
Journal of Virology; Chen J, Li Z et. al.

Apr 8th, 2022 - Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to pose an enormous threat to economic activity and public health worldwide. Previous studies have shown that the nonstructural protein 5 (nsp5, also called 3C-like protease) of alpha- and deltacoronaviruses cleaves Q231 of the NF-κB essential modulator (NEMO), a key kinase in the RIG-I-like receptor pathway, to inhibit type...

Structural basis for replicase polyprotein cleavage and substrate specificity of main p...
https://doi.org/10.1073/pnas.2117142119
Proceedings of the National Academy of Sciences of the Un... Zhao Y, Zhu Y et. al.

Apr 6th, 2022 - The main protease (Mpro) of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a key enzyme, which extensively digests CoV replicase polyproteins essential for viral replication and transcription, making it an attractive target for antiviral drug development. However, the molecular mechanism of how Mpro of SARS-CoV-2 digests replicase polyproteins, releasing the nonstructural prote...

Wolbachia depletion blocks transmission of lymphatic filariasis by preventing chitinase...
https://doi.org/10.1073/pnas.2120003119
Proceedings of the National Academy of Sciences of the Un... Quek S, Cook DAN et. al.

Apr 5th, 2022 - Lymphatic filariasis is a vector-borne neglected tropical disease prioritized for global elimination. The filarial nematodes that cause the disease host a symbiotic bacterium, Wolbachia, which has been targeted using antibiotics, leading to cessation of parasite embryogenesis, waning of circulating larvae (microfilariae [mf]), and gradual cure of adult infection. One of the benefits of the anti...

50S subunit recognition and modification by the Mycobacterium tuberculosis ribosomal RN...
https://doi.org/10.1073/pnas.2120352119
Proceedings of the National Academy of Sciences of the Un... Laughlin ZT, Nandi S et. al.

Apr 1st, 2022 - Changes in bacterial ribosomal RNA (rRNA) methylation status can alter the activity of diverse groups of ribosome-targeting antibiotics. These modifications are typically incorporated by a single methyltransferase that acts on one nucleotide target and rRNA methylation directly prevents drug binding, thereby conferring drug resistance. Loss of intrinsic methylation can also result in antibiotic...

An extended conformation of SARS-CoV-2 main protease reveals allosteric targets.
https://doi.org/10.1073/pnas.2120913119
Proceedings of the National Academy of Sciences of the Un... Sun Z, Wang L et. al.

Mar 25th, 2022 - SignificanceThe coronavirus main protease (Mpro) is required for viral replication. Here, we obtained the extended conformation of the native monomer of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Mpro by trapping it with nanobodies and found that the catalytic domain and the helix domain dissociate, revealing allosteric targets. Another monomeric state is termed compact confor...

Molecular characterization of a novel GSTO2 of Fasciola hepatica and its roles in modul...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8939299
Parasite (Paris, France); Wang X, Zhao C et. al.

Mar 23rd, 2022 - Fascioliasis is an important zoonotic helminthic disease caused by Fasciola hepatica and poses a serious threat to global public health. To evade the immune response of its host (humans or animals), F. hepatica secretes various antioxidant enzymes such as glutathione transferase (GST) to facilitate its invasion, migration and parasitism in vivo. To investigate the biological functions of a nove...

Identifying potential natural inhibitors of Brucella melitensis Methionyl-tRNA syntheta...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8970508
PLoS Neglected Tropical Diseases; Rowaiye AB, Ogugua AJ et. al.

Mar 22nd, 2022 - Brucellosis is an infectious disease caused by bacteria of the genus Brucella. Although it is the most common zoonosis worldwide, there are increasing reports of drug resistance and cases of relapse after long term treatment with the existing drugs of choice. This study therefore aims at identifying possible natural inhibitors of Brucella melitensis Methionyl-tRNA synthetase through an in-silic...

Phase II study of dichloroacetate, an inhibitor of pyruvate dehydrogenase, in combinati...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9106928
Investigational New Drugs; Powell SF, Mazurczak M et. al.

Mar 22nd, 2022 - Chemoradiotherapy (CRT) for locally-advanced head and neck squamous cell carcinoma (LA-HSNCC) yields 5-year survival rates near 50% despite causing significant toxicity. Dichloroacetate (DCA), a pyruvate dehydrogenase kinase metabolic inhibitor, reduces tumor lactate production and has been used in cancer therapy previously. The safety of adding this agent to CRT is unknown. Our randomized, pla...

The Glycolytic Gatekeeper PDK1 defines different metabolic states between genetically d...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8888573
Nature Communications; Erdem A, Marin S et. al.

Mar 3rd, 2022 - Acute myeloid leukemia remains difficult to treat due to strong genetic heterogeneity between and within individual patients. Here, we show that Pyruvate dehydrogenase kinase 1 (PDK1) acts as a targetable determinant of different metabolic states in acute myeloid leukemia (AML). PDK1low AMLs are OXPHOS-driven, are enriched for leukemic granulocyte-monocyte progenitor (L-GMP) signatures, and are...

Considerations on diagnosis and surveillance measures of PTEN hamartoma tumor syndrome:...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8886852
Orphanet Journal of Rare Diseases; Pena-Couso L, Ercibengoa M et. al.

Mar 2nd, 2022 - The limited knowledge about the PTEN hamartoma tumor syndrome (PHTS) makes its diagnosis a challenging task. We aimed to define the clinical and genetic characteristics of this syndrome in the Spanish population and to identify new genes potentially associated with the disease. We reviewed the clinical data collected through a specific questionnaire in a series of 145 Spanish patients with a ph...

Prevalence of Low Serum Alkaline Phosphatase and Hypophosphatasia in Adult Patients wit...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9108106
Calcified Tissue International; Tsiantouli E, Biver E et. al.

Mar 2nd, 2022 - Hypophosphatasia (HPP) is a rare genetic disorder characterized by low serum alkaline phosphatase (ALP), its manifestations may include atypical femoral fractures (AFF). However, the prevalence of low serum ALP and HPP in patients with AFF remains unknown. We retrospectively analyzed ALP levels and clinical manifestations compatible with HPP in 72 adult patients with confirmed AFF by chart revi...

Thyroid Follicular Cell-derived Carcinomas in a Background of Multiple Adenomatous Nodu...
https://doi.org/10.21873/anticanres.15619
Anticancer Research; Liu A, Borges PM et. al.

Feb 28th, 2022 - Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a complex disorder. Carriers develop hamartomatous tumors, with an increased risk for developing malignant tumors in multiple organs. Surveillance to facilitate the early detection and treatment of malignancies is extremely important. A 31-year-old male presented with a 10 cm left lobe thyroid gland mass. After fine needle...

Prognostic value of 11C-methionine volume-based PET parameters in IDH wild type gliobla...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8880430
PloS One; van Dijken BRJ, Ankrah AO et. al.

Feb 26th, 2022 - 11C-Methionine (11C-MET) PET prognostication of isocitrate dehydrogenase (IDH) wild type glioblastomas is inadequate as conventional parameters such as standardized uptake value (SUV) do not adequately reflect tumor heterogeneity. We retrospectively evaluated whether volume-based parameters such as metabolic tumor volume (MTV) and total lesion methionine metabolism (TLMM) outperformed SUV for s...

Do We Have Sufficient Evidence to Define Prognosis for "Low-grade" Fumarate Hydratase-d...
https://doi.org/10.1097/PAP.0000000000000335
Advances in Anatomic Pathology; Gupta S, Menon S et. al.

Feb 25th, 2022 - Do We Have Sufficient Evidence to Define Prognosis for "Low-grade" Fumarate Hydratase-deficient Renal Cell Carcinoma?|2022|Gupta S,Menon S,Raghunathan A,Herrera-Hernandez L,Jimenez RE,|diagnosis,enzymology,pathology,deficiency,genetics,diagnosis,enzymology,pathology,diagnosis,enzymology,pathology,diagnosis,enzymology,pathology,diagnosis,enzymology,pathology,