Hasty Briefsbeta

Bilingual

Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease - PubMed
6 days ago
- Inflammatory bowel disease (IBD) involves gut immune dysregulation, barrier dysfunction, and microbial imbalance, with bacterial dysbiosis well-studied.
- The gut virome and mycobiome are underexplored due to technical challenges like sequencing bias and incomplete databases.
- Fungal and viral dysbiosis are linked to IBD, including Candida overgrowth, loss of Saccharomyces, and expansion of specific phages and viruses.
- These alterations impact barrier integrity, immune signaling, and cross-kingdom interactions, amplifying inflammation.
- The virome and mycobiome offer therapeutic targets, such as probiotics, phage therapy, and fecal virome or microbiota transplantation.
- Research highlights the need for biomarker discovery and multikingdom microbiota-directed therapies in IBD.
Sialic acid cis-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity - PubMed
6 days ago
- Siglec-7 and -9 are glyco-immune checkpoints targeted in cancer immunotherapy.
- Cis-ligand interactions on immune cells inhibit trans-signaling induced by tumor cells.
- Co-blockade of both Siglec-7 and -9 enhances NK cell anti-tumor activity more than single blockade.
- Removing cis-ligands with sialidase further boosts NK cell killing of melanoma and AML cells.
- NK cell activation or proliferation downregulates Siglec-7 and -9 cis-ligand expression.
- Siglec-7/9 co-inhibition is key for clinical applications and next-generation immunotherapy design.
Specialized high-capacity mitochondria fuel cell invasion - PubMed
6 days ago
- Specialized mitochondria in C. elegans anchor cell localize to basement membrane breaching site.
- These high-capacity mitochondria have enriched electron transport chain components and dense cristae.
- Formation depends on AC specification and pro-invasive transcriptional program.
- Netrin signaling via Src kinase directs microtubule polarization for mitochondrial trafficking.
- High ATP production from these mitochondria fuels energetically intensive cell invasion.
Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival - PubMed
6 days ago
- Development of MethPro-LUAD, a prognostic model for lung adenocarcinoma based on eight 5-methylcytosine features.
- Model trained and tested using TCGA-LUAD data and validated across multiple independent cohorts and external datasets.
- Stratifies patients into high- and low-risk groups, with high-risk consistently showing shorter overall survival.
- Predictive performance remains robust across various subgroups and in disease-free survival analyses.
- Outperforms other reported prognostic models, offering potential for personalized treatment and clinical translation.
Complete biosynthesis of nicotine - PubMed
6 days ago
- The study identifies the final coupling reaction in nicotine biosynthesis, which is stabilized by glycosylation through a UDP-glycosyltransferase.
- Nicotine biosynthesis involves reduction and activation by A622, condensation via a stereoselective intermolecular Mannich-like reaction, oxidation by a berberine bridge enzyme-like (BBL) protein, and deglycosylation by a β-glucosidase.
- A 5-component metabolon assembles at vacuolar membranes to channel both nicotine biosynthesis and its transport, with reconstitution achieved in vitro and heterologously in vivo.
- Abrogating any of these components depletes nicotine accumulations, and a MATE transporter is essential for engineering nicotine production in heterologous plant species, conferring pest resistance.
- This work completes the nicotine biosynthesis pathway and provides insights into the intermolecular Mannich-like reaction, a key mechanism for scaffold formation in many plant alkaloids.
Distinct tissue niches contribute to prostate tissue-resident memory CD8+ T cell differentiation and heterogeneity - PubMed
6 days ago
- A protective and heterogeneous population of long-lived tissue-resident memory CD8+ T cells (Trm) forms in the prostate after acute infection in mice.
- Distinct stromal and glandular epithelial niches in the prostate drive phenotypic and functional diversity in Trm cells, with IL-15 and TGFβ highest in the epithelium, promoting persistence and cytotoxicity.
- Spatial transcriptomics provides a framework showing how localized signals in discrete tissue regions influence T cell fate and differentiation in both mice and humans.
Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth - PubMed
6 days ago
- A highly multiplexed antigen panel was used to analyze B cells from COVID-19 mRNA vaccinees, infected patients, and organ donors, identifying B cell subsets associated with variant binding breadth.
- Atypical B cells and a subset of class-switched memory B cells with recent germinal center exposure were enriched for antigen binding, with post-germinal center cells showing increased breadth and somatic hypermutation over time.
- mRNA vaccination preferentially stimulated B cells producing antibodies with inherently higher antigen-binding breadth compared to infection, highlighting key factors for vaccine design against rapidly mutating viruses.
Acute and chronic infections drive distinct trajectories in human memory CD4+ T cell formation - PubMed
6 days ago
- Acute and chronic infections lead to different developmental paths for human memory CD4+ T cells.
- In acute hepatitis C virus (HCV) infection, various progenitor CD4+ T cell subsets emerge, some of which also appear in chronic infection.
- In chronic HCV infection, stem-like Bcl-2+ CD4+ T cells and T-bet+ effector CD4+ T cells show a progenitor-progeny relationship.
- After therapy-mediated cure of HCV, CD4+ T cells retain a chronic infection signature but form a long-lasting, stable memory pool distinct from that after spontaneous clearance.
- The findings show that CD4+ T cell fates differ based on infection outcomes and reveal shared maintenance principles with exhausted CD8+ T cells during chronic infection.
A 10-Step Digital Workflow for Immediate Implant Placement and Loading in Terminal Dentition Patients - PubMed
6 days ago
- Proposes a 10-step digital workflow for immediate implant placement and loading in terminal dentition patients.
- Starts with acquiring and registering digital data to create a virtual patient model.
- Converts a 2D smile design to 3D to determine full-arch prosthesis type.
- Fuses CBCT and intraoral scan data to design the final prosthesis, considering post-extraction tissue changes.
- Plans implants, selects abutments and components, and designs a provisional prosthesis.
- Uses a stackable guide system for guided surgery to ensure precise implant placement and loading.
- Facilitates soft tissue healing according to the final design, crucial for FP1 restorations.
- Integrates technological advancements and a remodeling prediction algorithm for a systematic framework.
- Emphasizes a facially driven prosthetic design and thorough planning for functional and aesthetic outcomes.
- Provides a comprehensive treatment plan based on digital data analysis and prosthodontic/surgical principles.
Effect of a 5:2 intermittent fasting diet on obese patients with polycystic ovary syndrome - PubMed
6 days ago
- A 12-week 5:2 intermittent fasting diet with meal replacement significantly reduced body weight, BMI, and waist circumference in obese women with PCOS.
- Insulin resistance (HOMA-IR) and 2-hour glucose levels improved, but reproductive hormone levels did not show significant changes.
- Menstrual regularity improved in 80% of participants, and 50% showed improved ovulation frequency.
Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions - PubMed
6 days ago
- Researchers developed a multimodal spatial multi-omics framework integrating Visium HD, Xenium, and scRNA-seq to profile multiple myeloma (MM) interactions with the bone marrow microenvironment.
- The study identified plasma cell-dense niches enriched with non-canonical Wnt signaling, linked to drug resistance, poor survival, and extramedullary lesions.
- Immune cells within these niches showed suppressed states, including increased inhibitory receptors like LAG3, and a 15-gene signature from niche-driven states predicted progression-free survival.
Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis - PubMed
6 days ago
- TP53 mutations occur in 80-90% of triple-negative breast cancers (TNBCs) and drive genomic instability and metastasis.
- Mutant p53 (mtp53) associates with chromatin and PARP, enhancing PARP recruitment to replication forks to support S phase progression.
- The C-terminal domain of mtp53 is critical for its interaction with PARP and Poly (ADP-ribose) (PAR), facilitating tumor growth and metastasis.
- Combination therapy with PARP inhibitor talazoparib (TAL) and alkylating agent temozolomide (TMZ) selectively kills mtp53-expressing breast cancer cells and organoids.
- In preclinical models, TAL+TMZ treatment reduces circulating tumor cells, lung metastases, and metastasis-promoting proteins like MDMX in mtp53 tumors.
- Deletion of the mtp53 C-terminal domain impairs replication fork progression, tumor growth, and metastasis, highlighting its tumor-promoting role.
- Mutant p53 exploits PARP to enable adaptation to replication stress, making it a predictive biomarker for PARP inhibitor-based therapies in TNBC.
Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia - PubMed
6 days ago
- Frontotemporal dementia (FTD) is the second most common dementia after Alzheimer's disease, with GRN mutations being a major cause.
- TMEM106B genetic variants modify FTD risk, especially in GRN mutation carriers, and protective haplotypes can offer near lifetime protection.
- A C-terminal fragment of TMEM106B forms amyloid fibrils and accumulates in neurodegenerative disorders, including FTD.
- Granulin deficiency leads to accumulation of the TMEM106B C-terminal fragment in lysosomes in knockout mice and human iPSC-derived neurons.
- Progranulin supplementation reduces fragment accumulation, and TMEM106B risk alleles show allele-dose-dependent increases in fragments, reversible by progranulin.
- TMEM106B dimerization stabilizes the protein and limits fragment formation, linking granulin deficiency to fragment accumulation and explaining TMEM106B's role in FTD risk and protection.
STING causes replication stress and nascent DNA degradation via SAMHD1 - PubMed
6 days ago
- STING is an innate immune adaptor that can accumulate in the nucleus due to replication stress.
- Nuclear STING binds to nascent DNA and promotes replication stress in progeria and tumor cells.
- STING limits dNTP availability, causing replication fork slowing and stalling.
- STING facilitates MRE11-mediated nascent DNA degradation, hindering fork protection.
- SAMHD1 mediates STING's effects on dNTP depletion and nascent DNA degradation.
- Knockdown of SAMHD1 rescues replication fork speed and stability in STING-overexpressing cells.
- The STING-SAMHD1 axis drives replication stress and genome instability in progeria and tumor cells.
- A feedforward loop exists between innate immune signaling and impaired DNA replication.
Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting - PubMed
6 days ago
- IL-23 is a cytokine from the IL-12 family produced by antigen-presenting cells, central to adaptive immunity by promoting Th17 cell activity.
- In physiological conditions, IL-23 helps maintain pulmonary immune homeostasis and defends against bacterial and fungal pathogens.
- Dysregulated IL-23 signaling leads to chronic inflammation and tissue damage, playing a key role in the severity of various lung diseases.
- IL-23 is associated with increased disease severity, corticosteroid resistance, airway remodeling, and fibrosis in chronic lung conditions.
- The review discusses IL-23's role in chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, and COVID-19.
- Targeting IL-23 offers therapeutic potential for precision-guided strategies to modulate inflammation and remodeling, aided by biomarkers.
Pathology and genetics in a global cohort of Parkinsonian Disorders - PubMed
6 days ago
- Clinical misdiagnosis rates for movement disorders ranged from 10% to 20% in a large multi-ancestry brain bank cohort.
- Dementia with parkinsonism was more strongly associated with Lewy body pathology than Parkinson's disease without dementia.
- Alzheimer's disease co-pathology was present in 40% of cases with Lewy body disease.
- GBA1 variant carriers had greater Lewy body burden compared to noncarriers or LRRK2 carriers.
- Pathological diagnoses differed by ancestry, with South Asian donors more likely to have progressive supranuclear palsy and Ashkenazi Jewish donors more likely to have Lewy body disease.
- The findings support integrating genetic and pathological data to improve diagnostic accuracy and guide therapeutic trials.
Longitudinal Analysis of Superoxide Dismutase 1 Seeding Activity in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid - PubMed
6 days ago
- SOD1 seeding activity was detected in cerebrospinal fluid (CSF) of ALS patients, including those with and without SOD1 mutations, indicating misfolded SOD1 aggregates.
- In ALS progression, SOD1 seeding activity correlated with clinical decline measured by ALSFRS-R slope and increased CSF neurofilament light levels.
- SOD1 seeding activity was found early in the disease course in sporadic ALS patients, suggesting its potential as an early biomarker for clinical trial inclusion.
- The study highlights the potential of SOD1 seeding activity as a diagnostic, prognostic, and pharmacodynamic biomarker for SOD1-targeting therapies like tofersen, which could benefit a broader ALS population.
An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics - PubMed
6 days ago
- A preprint reports that a 12-week course of the FDA-approved antiretroviral regimen emtricitabine-tenofovir alafenamide (FTC/TAF) reduced measures of biological aging in healthy adults without HIV.
- Epigenetic clocks like DunedinPACE and PhenoAge showed significant decreases with FTC/TAF, alongside reductions in epigenetic proxies for inflammation such as IL-6, suggesting anti-aging effects.
- In contrast, a similar regimen using tenofovir disoproxil fumarate (FTC/TDF) did not show significant changes in aging markers, attributed to TAF's superior cellular pharmacology over TDF.
- This study provides the first human proof-of-concept for using retrotransposon-targeted therapies as gerotherapeutics, supporting further placebo-controlled trials with geroscience endpoints.
Clinical practice guidelines for postoperative pain management in adults (2024 edition) - PubMed
6 days ago
- The guidelines provide 33 evidence-based recommendations for 17 clinical questions on postoperative pain management in adults.
- Recommendations cover preoperative education, risk assessment, analgesic modality selection, and adverse effect management.
- Analgesia strategies include preemptive or multimodal analgesia, regional blocks, patient-controlled intravenous analgesia, and opioid-sparing techniques.
- The guidelines aim to standardize practices, enhance recovery after surgery, reduce opioid use, and shorten hospital stays.
- They are developed following WHO and Chinese guideline principles and are intended for healthcare professional reference, not as mandatory standards.
Reduced postprandial lipid accumulation in circulating monocytes by olezarsen attenuates pro-inflammatory changes in hypertriglyceridemic patients - PubMed
6 days ago
- Olezarsen is a drug that lowers fasting and postprandial triglycerides.
- In a trial with hypertriglyceridemic patients, olezarsen reduced postprandial triglyceride area under the curve by 55%.
- Olezarsen decreased intracellular lipid droplets in monocytes by 25.0% after a fat load.
- It reduced activation markers CD11c, CD11b, and CD16 in peripheral blood mononuclear cells.
- Postprandial interleukin-1beta gene expression in monocytes was lowered with olezarsen.
- Monocyte adhesion decreased by 14.4% in an ex vivo migration assay after treatment.
- Olezarsen attenuates pro-inflammatory changes by reducing lipid-driven immune-cell activation.

first prev19next

About|Login

Bilingual

Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease - PubMed
6 days ago
- Inflammatory bowel disease (IBD) involves gut immune dysregulation, barrier dysfunction, and microbial imbalance, with bacterial dysbiosis well-studied.
- The gut virome and mycobiome are underexplored due to technical challenges like sequencing bias and incomplete databases.
- Fungal and viral dysbiosis are linked to IBD, including Candida overgrowth, loss of Saccharomyces, and expansion of specific phages and viruses.
- These alterations impact barrier integrity, immune signaling, and cross-kingdom interactions, amplifying inflammation.
- The virome and mycobiome offer therapeutic targets, such as probiotics, phage therapy, and fecal virome or microbiota transplantation.
- Research highlights the need for biomarker discovery and multikingdom microbiota-directed therapies in IBD.
Sialic acid cis-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity - PubMed
6 days ago
- Siglec-7 and -9 are glyco-immune checkpoints targeted in cancer immunotherapy.
- Cis-ligand interactions on immune cells inhibit trans-signaling induced by tumor cells.
- Co-blockade of both Siglec-7 and -9 enhances NK cell anti-tumor activity more than single blockade.
- Removing cis-ligands with sialidase further boosts NK cell killing of melanoma and AML cells.
- NK cell activation or proliferation downregulates Siglec-7 and -9 cis-ligand expression.
- Siglec-7/9 co-inhibition is key for clinical applications and next-generation immunotherapy design.
Specialized high-capacity mitochondria fuel cell invasion - PubMed
6 days ago
- Specialized mitochondria in C. elegans anchor cell localize to basement membrane breaching site.
- These high-capacity mitochondria have enriched electron transport chain components and dense cristae.
- Formation depends on AC specification and pro-invasive transcriptional program.
- Netrin signaling via Src kinase directs microtubule polarization for mitochondrial trafficking.
- High ATP production from these mitochondria fuels energetically intensive cell invasion.
Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival - PubMed
6 days ago
- Development of MethPro-LUAD, a prognostic model for lung adenocarcinoma based on eight 5-methylcytosine features.
- Model trained and tested using TCGA-LUAD data and validated across multiple independent cohorts and external datasets.
- Stratifies patients into high- and low-risk groups, with high-risk consistently showing shorter overall survival.
- Predictive performance remains robust across various subgroups and in disease-free survival analyses.
- Outperforms other reported prognostic models, offering potential for personalized treatment and clinical translation.
Complete biosynthesis of nicotine - PubMed
6 days ago
- The study identifies the final coupling reaction in nicotine biosynthesis, which is stabilized by glycosylation through a UDP-glycosyltransferase.
- Nicotine biosynthesis involves reduction and activation by A622, condensation via a stereoselective intermolecular Mannich-like reaction, oxidation by a berberine bridge enzyme-like (BBL) protein, and deglycosylation by a β-glucosidase.
- A 5-component metabolon assembles at vacuolar membranes to channel both nicotine biosynthesis and its transport, with reconstitution achieved in vitro and heterologously in vivo.
- Abrogating any of these components depletes nicotine accumulations, and a MATE transporter is essential for engineering nicotine production in heterologous plant species, conferring pest resistance.
- This work completes the nicotine biosynthesis pathway and provides insights into the intermolecular Mannich-like reaction, a key mechanism for scaffold formation in many plant alkaloids.
Distinct tissue niches contribute to prostate tissue-resident memory CD8+ T cell differentiation and heterogeneity - PubMed
6 days ago
- A protective and heterogeneous population of long-lived tissue-resident memory CD8+ T cells (Trm) forms in the prostate after acute infection in mice.
- Distinct stromal and glandular epithelial niches in the prostate drive phenotypic and functional diversity in Trm cells, with IL-15 and TGFβ highest in the epithelium, promoting persistence and cytotoxicity.
- Spatial transcriptomics provides a framework showing how localized signals in discrete tissue regions influence T cell fate and differentiation in both mice and humans.
Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth - PubMed
6 days ago
- A highly multiplexed antigen panel was used to analyze B cells from COVID-19 mRNA vaccinees, infected patients, and organ donors, identifying B cell subsets associated with variant binding breadth.
- Atypical B cells and a subset of class-switched memory B cells with recent germinal center exposure were enriched for antigen binding, with post-germinal center cells showing increased breadth and somatic hypermutation over time.
- mRNA vaccination preferentially stimulated B cells producing antibodies with inherently higher antigen-binding breadth compared to infection, highlighting key factors for vaccine design against rapidly mutating viruses.
Acute and chronic infections drive distinct trajectories in human memory CD4+ T cell formation - PubMed
6 days ago
- Acute and chronic infections lead to different developmental paths for human memory CD4+ T cells.
- In acute hepatitis C virus (HCV) infection, various progenitor CD4+ T cell subsets emerge, some of which also appear in chronic infection.
- In chronic HCV infection, stem-like Bcl-2+ CD4+ T cells and T-bet+ effector CD4+ T cells show a progenitor-progeny relationship.
- After therapy-mediated cure of HCV, CD4+ T cells retain a chronic infection signature but form a long-lasting, stable memory pool distinct from that after spontaneous clearance.
- The findings show that CD4+ T cell fates differ based on infection outcomes and reveal shared maintenance principles with exhausted CD8+ T cells during chronic infection.
A 10-Step Digital Workflow for Immediate Implant Placement and Loading in Terminal Dentition Patients - PubMed
6 days ago
- Proposes a 10-step digital workflow for immediate implant placement and loading in terminal dentition patients.
- Starts with acquiring and registering digital data to create a virtual patient model.
- Converts a 2D smile design to 3D to determine full-arch prosthesis type.
- Fuses CBCT and intraoral scan data to design the final prosthesis, considering post-extraction tissue changes.
- Plans implants, selects abutments and components, and designs a provisional prosthesis.
- Uses a stackable guide system for guided surgery to ensure precise implant placement and loading.
- Facilitates soft tissue healing according to the final design, crucial for FP1 restorations.
- Integrates technological advancements and a remodeling prediction algorithm for a systematic framework.
- Emphasizes a facially driven prosthetic design and thorough planning for functional and aesthetic outcomes.
- Provides a comprehensive treatment plan based on digital data analysis and prosthodontic/surgical principles.
Effect of a 5:2 intermittent fasting diet on obese patients with polycystic ovary syndrome - PubMed
6 days ago
- A 12-week 5:2 intermittent fasting diet with meal replacement significantly reduced body weight, BMI, and waist circumference in obese women with PCOS.
- Insulin resistance (HOMA-IR) and 2-hour glucose levels improved, but reproductive hormone levels did not show significant changes.
- Menstrual regularity improved in 80% of participants, and 50% showed improved ovulation frequency.
Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions - PubMed
6 days ago
- Researchers developed a multimodal spatial multi-omics framework integrating Visium HD, Xenium, and scRNA-seq to profile multiple myeloma (MM) interactions with the bone marrow microenvironment.
- The study identified plasma cell-dense niches enriched with non-canonical Wnt signaling, linked to drug resistance, poor survival, and extramedullary lesions.
- Immune cells within these niches showed suppressed states, including increased inhibitory receptors like LAG3, and a 15-gene signature from niche-driven states predicted progression-free survival.
Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis - PubMed
6 days ago
- TP53 mutations occur in 80-90% of triple-negative breast cancers (TNBCs) and drive genomic instability and metastasis.
- Mutant p53 (mtp53) associates with chromatin and PARP, enhancing PARP recruitment to replication forks to support S phase progression.
- The C-terminal domain of mtp53 is critical for its interaction with PARP and Poly (ADP-ribose) (PAR), facilitating tumor growth and metastasis.
- Combination therapy with PARP inhibitor talazoparib (TAL) and alkylating agent temozolomide (TMZ) selectively kills mtp53-expressing breast cancer cells and organoids.
- In preclinical models, TAL+TMZ treatment reduces circulating tumor cells, lung metastases, and metastasis-promoting proteins like MDMX in mtp53 tumors.
- Deletion of the mtp53 C-terminal domain impairs replication fork progression, tumor growth, and metastasis, highlighting its tumor-promoting role.
- Mutant p53 exploits PARP to enable adaptation to replication stress, making it a predictive biomarker for PARP inhibitor-based therapies in TNBC.
Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia - PubMed
6 days ago
- Frontotemporal dementia (FTD) is the second most common dementia after Alzheimer's disease, with GRN mutations being a major cause.
- TMEM106B genetic variants modify FTD risk, especially in GRN mutation carriers, and protective haplotypes can offer near lifetime protection.
- A C-terminal fragment of TMEM106B forms amyloid fibrils and accumulates in neurodegenerative disorders, including FTD.
- Granulin deficiency leads to accumulation of the TMEM106B C-terminal fragment in lysosomes in knockout mice and human iPSC-derived neurons.
- Progranulin supplementation reduces fragment accumulation, and TMEM106B risk alleles show allele-dose-dependent increases in fragments, reversible by progranulin.
- TMEM106B dimerization stabilizes the protein and limits fragment formation, linking granulin deficiency to fragment accumulation and explaining TMEM106B's role in FTD risk and protection.
STING causes replication stress and nascent DNA degradation via SAMHD1 - PubMed
6 days ago
- STING is an innate immune adaptor that can accumulate in the nucleus due to replication stress.
- Nuclear STING binds to nascent DNA and promotes replication stress in progeria and tumor cells.
- STING limits dNTP availability, causing replication fork slowing and stalling.
- STING facilitates MRE11-mediated nascent DNA degradation, hindering fork protection.
- SAMHD1 mediates STING's effects on dNTP depletion and nascent DNA degradation.
- Knockdown of SAMHD1 rescues replication fork speed and stability in STING-overexpressing cells.
- The STING-SAMHD1 axis drives replication stress and genome instability in progeria and tumor cells.
- A feedforward loop exists between innate immune signaling and impaired DNA replication.
Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting - PubMed
6 days ago
- IL-23 is a cytokine from the IL-12 family produced by antigen-presenting cells, central to adaptive immunity by promoting Th17 cell activity.
- In physiological conditions, IL-23 helps maintain pulmonary immune homeostasis and defends against bacterial and fungal pathogens.
- Dysregulated IL-23 signaling leads to chronic inflammation and tissue damage, playing a key role in the severity of various lung diseases.
- IL-23 is associated with increased disease severity, corticosteroid resistance, airway remodeling, and fibrosis in chronic lung conditions.
- The review discusses IL-23's role in chronic obstructive pulmonary disease, asthma, idiopathic pulmonary fibrosis, and COVID-19.
- Targeting IL-23 offers therapeutic potential for precision-guided strategies to modulate inflammation and remodeling, aided by biomarkers.
Pathology and genetics in a global cohort of Parkinsonian Disorders - PubMed
6 days ago
- Clinical misdiagnosis rates for movement disorders ranged from 10% to 20% in a large multi-ancestry brain bank cohort.
- Dementia with parkinsonism was more strongly associated with Lewy body pathology than Parkinson's disease without dementia.
- Alzheimer's disease co-pathology was present in 40% of cases with Lewy body disease.
- GBA1 variant carriers had greater Lewy body burden compared to noncarriers or LRRK2 carriers.
- Pathological diagnoses differed by ancestry, with South Asian donors more likely to have progressive supranuclear palsy and Ashkenazi Jewish donors more likely to have Lewy body disease.
- The findings support integrating genetic and pathological data to improve diagnostic accuracy and guide therapeutic trials.
Longitudinal Analysis of Superoxide Dismutase 1 Seeding Activity in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid - PubMed
6 days ago
- SOD1 seeding activity was detected in cerebrospinal fluid (CSF) of ALS patients, including those with and without SOD1 mutations, indicating misfolded SOD1 aggregates.
- In ALS progression, SOD1 seeding activity correlated with clinical decline measured by ALSFRS-R slope and increased CSF neurofilament light levels.
- SOD1 seeding activity was found early in the disease course in sporadic ALS patients, suggesting its potential as an early biomarker for clinical trial inclusion.
- The study highlights the potential of SOD1 seeding activity as a diagnostic, prognostic, and pharmacodynamic biomarker for SOD1-targeting therapies like tofersen, which could benefit a broader ALS population.
An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics - PubMed
6 days ago
- A preprint reports that a 12-week course of the FDA-approved antiretroviral regimen emtricitabine-tenofovir alafenamide (FTC/TAF) reduced measures of biological aging in healthy adults without HIV.
- Epigenetic clocks like DunedinPACE and PhenoAge showed significant decreases with FTC/TAF, alongside reductions in epigenetic proxies for inflammation such as IL-6, suggesting anti-aging effects.
- In contrast, a similar regimen using tenofovir disoproxil fumarate (FTC/TDF) did not show significant changes in aging markers, attributed to TAF's superior cellular pharmacology over TDF.
- This study provides the first human proof-of-concept for using retrotransposon-targeted therapies as gerotherapeutics, supporting further placebo-controlled trials with geroscience endpoints.
Clinical practice guidelines for postoperative pain management in adults (2024 edition) - PubMed
6 days ago
- The guidelines provide 33 evidence-based recommendations for 17 clinical questions on postoperative pain management in adults.
- Recommendations cover preoperative education, risk assessment, analgesic modality selection, and adverse effect management.
- Analgesia strategies include preemptive or multimodal analgesia, regional blocks, patient-controlled intravenous analgesia, and opioid-sparing techniques.
- The guidelines aim to standardize practices, enhance recovery after surgery, reduce opioid use, and shorten hospital stays.
- They are developed following WHO and Chinese guideline principles and are intended for healthcare professional reference, not as mandatory standards.
Reduced postprandial lipid accumulation in circulating monocytes by olezarsen attenuates pro-inflammatory changes in hypertriglyceridemic patients - PubMed
6 days ago
- Olezarsen is a drug that lowers fasting and postprandial triglycerides.
- In a trial with hypertriglyceridemic patients, olezarsen reduced postprandial triglyceride area under the curve by 55%.
- Olezarsen decreased intracellular lipid droplets in monocytes by 25.0% after a fat load.
- It reduced activation markers CD11c, CD11b, and CD16 in peripheral blood mononuclear cells.
- Postprandial interleukin-1beta gene expression in monocytes was lowered with olezarsen.
- Monocyte adhesion decreased by 14.4% in an ex vivo migration assay after treatment.
- Olezarsen attenuates pro-inflammatory changes by reducing lipid-driven immune-cell activation.

Hasty Briefsbeta

Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease - PubMed

Sialic acid cis-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity - PubMed

Specialized high-capacity mitochondria fuel cell invasion - PubMed

Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival - PubMed

Complete biosynthesis of nicotine - PubMed

Distinct tissue niches contribute to prostate tissue-resident memory CD8+ T cell differentiation and heterogeneity - PubMed

Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth - PubMed

Acute and chronic infections drive distinct trajectories in human memory CD4+ T cell formation - PubMed

A 10-Step Digital Workflow for Immediate Implant Placement and Loading in Terminal Dentition Patients - PubMed

Effect of a 5:2 intermittent fasting diet on obese patients with polycystic ovary syndrome - PubMed

Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions - PubMed

Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis - PubMed

Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia - PubMed

STING causes replication stress and nascent DNA degradation via SAMHD1 - PubMed

Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting - PubMed

Pathology and genetics in a global cohort of Parkinsonian Disorders - PubMed

Longitudinal Analysis of Superoxide Dismutase 1 Seeding Activity in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid - PubMed

An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics - PubMed

Clinical practice guidelines for postoperative pain management in adults (2024 edition) - PubMed

Reduced postprandial lipid accumulation in circulating monocytes by olezarsen attenuates pro-inflammatory changes in hypertriglyceridemic patients - PubMed

Neglected kingdoms: the gut virome, mycobiome and their role in inflammatory bowel disease - PubMed

Sialic acid cis-ligand dynamics modulate Siglec-7 and -9 function and affect Siglec-7/9 co-blockade to potentiate natural killer cell anti-tumor activity - PubMed

Specialized high-capacity mitochondria fuel cell invasion - PubMed

Development and validation of a 5mC-based prognostic model for lung adenocarcinoma survival - PubMed

Complete biosynthesis of nicotine - PubMed

Distinct tissue niches contribute to prostate tissue-resident memory CD8+ T cell differentiation and heterogeneity - PubMed

Multiplexed antigen panel analysis identifies B cell phenotype and receptor genetic contributions to antibody breadth - PubMed

Acute and chronic infections drive distinct trajectories in human memory CD4+ T cell formation - PubMed

A 10-Step Digital Workflow for Immediate Implant Placement and Loading in Terminal Dentition Patients - PubMed

Effect of a 5:2 intermittent fasting diet on obese patients with polycystic ovary syndrome - PubMed

Spatial multi-omics of multiple myeloma uncovers niche-dependent pro-myeloma and immunosuppressive signaling in the bone marrow and extramedullary lesions - PubMed

Mutant p53 Directs PARP to Regulate Replication Stress and Drive Breast Cancer Metastasis - PubMed

Granulin loss and TMEM106B risk converge on lysosomal C-terminal fragment pathology in frontotemporal dementia - PubMed

STING causes replication stress and nascent DNA degradation via SAMHD1 - PubMed

Interleukin-23 in lung and airway diseases: from pathogenesis to precision-guided therapeutic targeting - PubMed

Pathology and genetics in a global cohort of Parkinsonian Disorders - PubMed

Longitudinal Analysis of Superoxide Dismutase 1 Seeding Activity in Amyotrophic Lateral Sclerosis Cerebrospinal Fluid - PubMed

An FDA-Approved Tenofovir Alafenamide-Based Antiretroviral Therapy Reduces Biological Age in Healthy Adults: First Human Proof-of-Concept for Retrotransposon-Targeted Gerotherapeutics - PubMed

Clinical practice guidelines for postoperative pain management in adults (2024 edition) - PubMed

Reduced postprandial lipid accumulation in circulating monocytes by olezarsen attenuates pro-inflammatory changes in hypertriglyceridemic patients - PubMed