Hasty Briefsbeta

Bilingual

Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data - PubMed
5 days ago
- A UK Biobank study with 121,017 postmenopausal women aged 40-69 linked earlier menopause to increased risks of developing the first chronic disease (FCD) and progressing to multimorbidity.
- Over a median follow-up of 8.6 years, risks from health to FCD were higher in women with premature (HR=1.32), early (HR=1.14), and relatively early menopause (HR=1.03) compared to menopause after age 50.
- For transitions from FCD to multimorbidity, risks also increased: premature (HR=1.22), early (HR=1.13), and relatively early menopause (HR=1.06).
- The study concluded that earlier menopause is associated with greater multimorbidity and mortality risks, particularly in trajectories from health to FCD and from FCD to multimorbidity.
New insights in multiple sclerosis pathology - PubMed
5 days ago
- Relapse-associated worsening and progression independent of relapse activity both contribute to long-term disability in multiple sclerosis (MS).
- Tissue resident memory cells and microglia are key drivers of persistent CNS inflammation and disease progression.
- Soluble factors, including interferon γ, play a detrimental role in neuronal injury, synapse damage, and impaired remyelination.
- Modern -omics approaches (e.g., snRNA sequencing, spatial transcriptomics) have advanced understanding of immune-neural interactions in MS.
- Insights from human tissue studies may lead to novel therapies targeting CNS inflammation, neurodegeneration, and promoting remyelination.
Prospective real-world experience with risankizumab in difficult-to-treat Crohn's disease: results from the Dutch Initiative on Crohn and Colitis Registry - PubMed
5 days ago
- Risankizumab, an IL-23 inhibitor, was evaluated in a real-world study for difficult-to-treat Crohn's disease.
- The study included 151 patients, with 90.1% having difficult-to-treat disease (failure of ≥2 advanced therapies).
- At week 24, 50% of patients with active disease achieved corticosteroid-free clinical remission.
- In patients with difficult-to-treat disease specifically, 51.8% achieved corticosteroid-free clinical remission at week 24.
- Treatment discontinuation occurred in 14.6% of patients, primarily due to nonresponse.
- Adverse event rates were 35.3 (possibly related) and 16.6 (probably related) per 100 person-years.
- Risankizumab demonstrated favorable effectiveness and safety, supporting its use in difficult-to-treat cases.
Adverse events after Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System, 2024-2025, United States - PubMed
5 days ago
- The study analyzed adverse events (AEs) reported to the U.S. VAERS for Pfizer's RSV vaccine (Abrysvo) in pregnant women during the 2024-2025 RSV season.
- A total of 131 reports were received; 46 (35%) described injection site and systemic reactions.
- The most common pregnancy-specific outcomes were preterm birth (15 cases, 11%) and hypertensive disorders of pregnancy (9 cases, 7%).
- The reported AEs were consistent with prelicensure studies, supporting the vaccine's safety profile as recommended for pregnant women at 32-36 weeks' gestation.
Integrating network toxicology and experimental validation reveals the immunotoxic effects of acetylcitric acid tributyl ester on systemic lupus erythematosus - PubMed
5 days ago
- Study uses network toxicology and experiments to show acetyl tributyl citrate (ATBC) worsens immune toxicity in systemic lupus erythematosus (SLE).
- ATBC binds to key proteins like STAT3, BCL2, and GSK3β, with lower toxicity thresholds in SLE patient cells (IC50 49.8 μM) than healthy cells (68.7 μM).
- Exposure increases oxidative stress and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-6) while reducing anti-inflammatory IL-10, especially in SLE.
- Mechanism involves ROS-induced DNA damage and reduced TREX1, activating the cGAS-STING pathway and disrupting survival/inflammatory markers.
- Findings highlight ATBC as an environmental trigger for SLE via redox imbalance and DNA-sensing, assessing risks of 'safe' plasticizers in autoimmune diseases.
Molecular pathways driving clarithromycin benefit in community-acquired pneumonia: analysis of the ACCESS randomised trial - PubMed
5 days ago
- The ACCESS trial showed that adding clarithromycin to standard care in hospitalized CAP patients led to earlier symptom resolution and reduced progression to respiratory failure and sepsis.
- Gene expression analysis indicated clarithromycin upregulated genes involved in T-cell activation and MHC II expression, while downregulating IL-1 receptors and neutrophil degranulation pathways.
- Clarithromycin treatment was associated with decreased IL-1 cytokine production (linked to respiratory failure) and increased monocyte-derived pro-inflammatory cytokines and chemokines (linked to clinical benefit), alongside attenuated anti-inflammatory cytokine production.
- The study concludes that clarithromycin's clinical benefits in CAP may stem from modulating immune pathways, including attenuating IL-1, enhancing antigen presentation, and reducing neutrophil degranulation.
Maternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions - PubMed
5 days ago
- Maternal nutrition impacts the protective functions of the placenta and developing blood-brain barrier (BBB) against xenobiotics.
- Both undernutrition and overnutrition/obesity remodel placental morphology, impair barrier efficiency, and weaken efflux transporters like P-gp, BCRP, and MRP2.
- Nutritional imbalances dysregulate nutrient transporters (e.g., GLUT1, SNATs, LATs, FATP/CD36), increasing risks for adverse developmental programming.
- Maternal nutritional adversity is linked to increased BBB permeability, reduced efflux capacity, and compromised tight junction integrity.
- Micronutrients (e.g., copper, folate, iron, vitamins A, B12, D, zinc) are crucial regulators of BBB efflux transporter activity and junctional stability.
- Optimizing maternal diet before and during pregnancy can reinforce these barriers, safeguard the fetal brain, and improve long-term offspring health.
Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy - PubMed
5 days ago
- BCMA expression at baseline is universal but heterogeneous in patients with relapsed/refractory multiple myeloma.
- High BCMA expression by flow cytometry correlates with better clinical outcomes, including deeper responses and longer time to progression.
- BCMA loss is rare at relapse, but decreased expression is common, with half of paired samples showing downregulation.
- Flow cytometry and immunohistochemistry show poor concordance in categorizing BCMA expression levels.
- Retained BCMA expression at relapse suggests potential for sequencing BCMA-directed therapies.
Macrophage-derived extracellular vesicles in the remodeling of the prostate cancer immune microenvironment and therapeutic resistance - PubMed
5 days ago
- The article discusses the role of macrophage-derived extracellular vesicles in reshaping the prostate cancer immune microenvironment and contributing to therapeutic resistance.
- Keywords include Extracellular vesicle, Immune microenvironment, Prostate cancer, Therapeutic resistance, and Tumor-associated macrophage, indicating the main focus areas.
- No conflicts of interest were declared by the authors, and ethical approvals or consents were noted as not applicable for this study.
- The references provide context through related studies on biomarkers, PET imaging, and immune mechanisms in prostate cancer progression and treatment.
Cardiovascular pharmacotherapy in year in 2025 - PubMed
5 days ago
- Four new drugs were approved: aficamten, etripamil, lerodalcibep, and plozasiran.
- Label expansions occurred for five already approved drugs.
- Results from major randomized clinical trials included both positive and neutral/negative outcomes.
- Andexanet-alfa was withdrawn from the U.S. market due to safety concerns.
- Promising experimental cardiovascular drugs are in ongoing phase 2 and 3 trials.
Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review - PubMed
5 days ago
- Mitochondrial dysfunction is central to age-related macular degeneration (AMD), particularly affecting the retinal pigment epithelium (RPE).
- Dysregulation of mitochondrial dynamics—fission, fusion, biogenesis, and mitophagy—leads to fragmented and dysfunctional mitochondria in AMD.
- Consequences include bioenergetic deficits, oxidative stress, and inflammation, driving AMD pathology.
- Therapeutic strategies targeting mitochondrial pathways, such as antioxidants and dynamic modulators, show promise for intervention.
- Future advances in biomarkers and personalized approaches may address root causes of AMD.
Myricetin stabilizes PINK1 to activate mitophagy and ameliorate metabolic dysfunction-associated steatotic liver disease - PubMed
5 days ago
- Myricetin is a bioactive flavonoid from Abelmoschus manihot that shows therapeutic potential for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, MASH.
- Myricetin treatment ameliorated hepatic steatosis, inflammation, fibrosis, and insulin resistance in mouse models of MASLD/MASH induced by high-fat or GAN diets.
- Transcriptomic analysis revealed enhanced fatty acid β-oxidation and mitochondrial function after myricetin administration.
- Myricetin directly binds to PINK1, stabilizing it on the outer mitochondrial membrane by inhibiting import through TOM40 and cleavage by PARL protease.
- Stabilized PINK1 activates PINK1/Parkin-dependent mitophagy, restoring mitochondrial integrity and quality.
- Silencing PINK1 abolished myricetin's benefits, confirming the mechanism involving PINK1 stabilization and mitophagy activation.
Zuogui pill ameliorates DNA damage and the senescence-associated secretory phenotype in ovarian stem cells to delay ovarian ageing through activation of SIRT1 - PubMed
5 days ago
- Zuogui Pill (ZGP) delays ovarian aging by enhancing ovarian stem cell (OSC) stemness, increasing follicle count, and raising serum AMH and E2 levels.
- ZGP upregulates SIRT1 to suppress DNA damage (γ-H2AX and CHEK2) and modulate acetylation of Ku70 and p65, reducing p53/p21 expression and SASP.
- The study employs bioinformatics (WGCNA, network pharmacology) and experimental validation in mice and D-gal-induced OSC models to confirm SIRT1-dependent mechanisms.
Gut-derived IL-17A via STAT3/RORγt signaling underlies sleep disruption-induced depression: Targeting effects of Schisandrin B therapy - PubMed
5 days ago
- Sleep disruption induces depression through gut-derived IL-17A signaling via STAT3/RORγt, leading to neuroinflammation.
- Schisandrin B, from Schisandra chinensis, reverses depressive behaviors by restoring gut-brain axis balance and suppressing IL-17A inflammation.
- Clinical and mouse studies show elevated IL-17A and metabolic issues in depression, with Schisandrin B improving gut barrier and neural function.
- Schisandrin B targets MAPK1 and GSK3β, inhibiting STAT3/RORγt, highlighting its potential as a natural immunomodulatory therapy for mood disorders.
Informal caregivers' preferences for self-care support services in caring for community-dwelling older adults with disabilities: A discrete choice experiment - PubMed
5 days ago
- Informal caregivers prioritize self-care support services, especially frequent respite and comprehensive health guidance, over cost considerations.
- A discrete choice experiment with 226 caregivers in Qingdao, China, identified respite service frequency (24.0% relative importance) and health guidance content (21.7%) as the most influential attributes.
- Caregivers' willingness-to-pay was estimated at ¥3132.48 monthly for weekly respite and ¥2827.48 for comprehensive health guidance, showing minimal influence from cost (0.01%).
- Significant preference heterogeneity exists, linked to sociodemographic factors, health status, stress levels, and patient outcomes, highlighting the need for individualized support.
- Community nurses are crucial for assessing caregiver strain, delivering tailored guidance, coordinating services, and ensuring equitable access to enhance caregiver sustainability and care quality.
Gut microbiota and pattern recognition receptors in polycystic ovary syndrome - PubMed
5 days ago
- PCOS is recognized as a disorder of impaired immune-endocrine homeostasis.
- Gut dysbiosis and microbial metabolite imbalance activate pattern recognition receptors (PRRs), forming a PRR-microbiota-reproductive axis.
- Gut-derived signals like LPS and SCFAs modulate TLR, NLR, and RLR pathways, disrupting immune regulation.
- The Reproductive Immune Tolerance Disruption Theory proposes chronic PRR activation shifts reproductive immunity to a low-grade inflammatory state.
- This inflammation promotes hyperandrogenism, anovulation, insulin resistance, and metabolic dysfunction in PCOS.
- Multi-omics studies clarify crosstalk between gut microbial signatures and innate immune signaling.
- Potential therapies include PRR-selective immunomodulation, microbiota-based treatments, and epigenetic metabolic interventions.
- Understanding PRR-driven immunomodulation helps reconcile endocrine, metabolic, and reproductive abnormalities in PCOS.
LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing - PubMed
5 days ago
- LINC00607 is a long non-coding RNA that regulates alternative splicing of the VEGF receptor FLT1 in endothelial cells, influencing angiogenesis.
- Knockout of LINC00607 increases production of soluble FLT1 (sFLT1), a decoy receptor that inhibits VEGF signaling and impairs angiogenesis, which can be reversed with sFLT1-neutralizing antibodies.
- LINC00607 interacts with U2 snRNA and depends on the chromatin remodeler BRG1 to prevent exon 15 inclusion in FLT1, thus reducing sFLT1 formation.
- A splice-blocking morpholino targeting the FLT1 intron14/exon15 junction reduces sFLT1 production and enhances VEGF-A-mediated sprouting by interacting with LINC00607 and U2 snRNA.
- LINC00607 expression is downregulated in preeclampsia and inversely correlates with sFLT1 levels in vascular diseases, suggesting a role in the pathophysiology of conditions like preeclampsia.
Autologous CD19 CAR T-cell therapy for pediatric and adult systemic lupus erythematosus: a phase 1/2 trial - PubMed
5 days ago
- The trial evaluates autologous CD19 CAR T-cell therapy for systemic lupus erythematosus in a phase 1/2 design.
- Primary endpoints focus on dose-limiting toxicity and adverse events in phase 1, and response rates at 3 and 6 months in phase 2.
- Eighteen patients were enrolled, mostly pediatric, with 15 having a SLEDAI-2K score ≥4.
- No dose-limiting toxicities occurred, and the recommended dose for phase 2 was 1×10^6 CAR T cells/kg.
- Adverse events included grade 1 cytokine release syndrome in 72%, neurotoxicity in 17%, and infections in 17%.
- Response rates at month 3 and 6 for patients with SLEDAI-2K ≥4 were 9 out of 15 and 12 out of 15 achieving SRI-S response, with some achieving LLDAS or DORIS remission.
- Median follow-up was 10.2 months, with most responders maintaining response without immunosuppressants, and CAR T cells persisted for a median of 56 days.
An in vivo CRISPR screen unveils promising target genes to improve CAR-T cell efficacy in a solid tumor model - PubMed
5 days ago
- CAR-T cell therapies face limitations, including poor persistence and inefficacy against solid tumors.
- An in vivo CRISPR screen targeting 50 genes identified REGNASE-1, SOCS1, PTPN2, and P16INK4A as top targets to enhance CAR-T cell persistence in a lung tumor model.
- Disruption of genes like MED12, PRDM1, and BATF, previously thought beneficial, was detrimental in this context, indicating context-dependent effects.
- The study underscores the need for context-specific evaluations of genetic modifications to optimize CAR-T therapies for clinical translation.
SARS-CoV-2 directly infects the inner ear and causes hearing dysfunction - PubMed
5 days ago
- SARS-CoV-2 infects inner ear spiral ganglion neurons in mice, leading to hearing dysfunction.
- Spike protein overexpression disrupts stress granule regulation via mTOR inhibition, causing neuronal phase separation and apoptosis.
- Findings suggest an inflammation-independent pathway for COVID-19-related hearing loss.

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Bilingual

Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data - PubMed
5 days ago
- A UK Biobank study with 121,017 postmenopausal women aged 40-69 linked earlier menopause to increased risks of developing the first chronic disease (FCD) and progressing to multimorbidity.
- Over a median follow-up of 8.6 years, risks from health to FCD were higher in women with premature (HR=1.32), early (HR=1.14), and relatively early menopause (HR=1.03) compared to menopause after age 50.
- For transitions from FCD to multimorbidity, risks also increased: premature (HR=1.22), early (HR=1.13), and relatively early menopause (HR=1.06).
- The study concluded that earlier menopause is associated with greater multimorbidity and mortality risks, particularly in trajectories from health to FCD and from FCD to multimorbidity.
New insights in multiple sclerosis pathology - PubMed
5 days ago
- Relapse-associated worsening and progression independent of relapse activity both contribute to long-term disability in multiple sclerosis (MS).
- Tissue resident memory cells and microglia are key drivers of persistent CNS inflammation and disease progression.
- Soluble factors, including interferon γ, play a detrimental role in neuronal injury, synapse damage, and impaired remyelination.
- Modern -omics approaches (e.g., snRNA sequencing, spatial transcriptomics) have advanced understanding of immune-neural interactions in MS.
- Insights from human tissue studies may lead to novel therapies targeting CNS inflammation, neurodegeneration, and promoting remyelination.
Prospective real-world experience with risankizumab in difficult-to-treat Crohn's disease: results from the Dutch Initiative on Crohn and Colitis Registry - PubMed
5 days ago
- Risankizumab, an IL-23 inhibitor, was evaluated in a real-world study for difficult-to-treat Crohn's disease.
- The study included 151 patients, with 90.1% having difficult-to-treat disease (failure of ≥2 advanced therapies).
- At week 24, 50% of patients with active disease achieved corticosteroid-free clinical remission.
- In patients with difficult-to-treat disease specifically, 51.8% achieved corticosteroid-free clinical remission at week 24.
- Treatment discontinuation occurred in 14.6% of patients, primarily due to nonresponse.
- Adverse event rates were 35.3 (possibly related) and 16.6 (probably related) per 100 person-years.
- Risankizumab demonstrated favorable effectiveness and safety, supporting its use in difficult-to-treat cases.
Adverse events after Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System, 2024-2025, United States - PubMed
5 days ago
- The study analyzed adverse events (AEs) reported to the U.S. VAERS for Pfizer's RSV vaccine (Abrysvo) in pregnant women during the 2024-2025 RSV season.
- A total of 131 reports were received; 46 (35%) described injection site and systemic reactions.
- The most common pregnancy-specific outcomes were preterm birth (15 cases, 11%) and hypertensive disorders of pregnancy (9 cases, 7%).
- The reported AEs were consistent with prelicensure studies, supporting the vaccine's safety profile as recommended for pregnant women at 32-36 weeks' gestation.
Integrating network toxicology and experimental validation reveals the immunotoxic effects of acetylcitric acid tributyl ester on systemic lupus erythematosus - PubMed
5 days ago
- Study uses network toxicology and experiments to show acetyl tributyl citrate (ATBC) worsens immune toxicity in systemic lupus erythematosus (SLE).
- ATBC binds to key proteins like STAT3, BCL2, and GSK3β, with lower toxicity thresholds in SLE patient cells (IC50 49.8 μM) than healthy cells (68.7 μM).
- Exposure increases oxidative stress and pro-inflammatory cytokines (IFN-γ, TNF-α, IL-2, IL-6) while reducing anti-inflammatory IL-10, especially in SLE.
- Mechanism involves ROS-induced DNA damage and reduced TREX1, activating the cGAS-STING pathway and disrupting survival/inflammatory markers.
- Findings highlight ATBC as an environmental trigger for SLE via redox imbalance and DNA-sensing, assessing risks of 'safe' plasticizers in autoimmune diseases.
Molecular pathways driving clarithromycin benefit in community-acquired pneumonia: analysis of the ACCESS randomised trial - PubMed
5 days ago
- The ACCESS trial showed that adding clarithromycin to standard care in hospitalized CAP patients led to earlier symptom resolution and reduced progression to respiratory failure and sepsis.
- Gene expression analysis indicated clarithromycin upregulated genes involved in T-cell activation and MHC II expression, while downregulating IL-1 receptors and neutrophil degranulation pathways.
- Clarithromycin treatment was associated with decreased IL-1 cytokine production (linked to respiratory failure) and increased monocyte-derived pro-inflammatory cytokines and chemokines (linked to clinical benefit), alongside attenuated anti-inflammatory cytokine production.
- The study concludes that clarithromycin's clinical benefits in CAP may stem from modulating immune pathways, including attenuating IL-1, enhancing antigen presentation, and reducing neutrophil degranulation.
Maternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions - PubMed
5 days ago
- Maternal nutrition impacts the protective functions of the placenta and developing blood-brain barrier (BBB) against xenobiotics.
- Both undernutrition and overnutrition/obesity remodel placental morphology, impair barrier efficiency, and weaken efflux transporters like P-gp, BCRP, and MRP2.
- Nutritional imbalances dysregulate nutrient transporters (e.g., GLUT1, SNATs, LATs, FATP/CD36), increasing risks for adverse developmental programming.
- Maternal nutritional adversity is linked to increased BBB permeability, reduced efflux capacity, and compromised tight junction integrity.
- Micronutrients (e.g., copper, folate, iron, vitamins A, B12, D, zinc) are crucial regulators of BBB efflux transporter activity and junctional stability.
- Optimizing maternal diet before and during pregnancy can reinforce these barriers, safeguard the fetal brain, and improve long-term offspring health.
Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy - PubMed
5 days ago
- BCMA expression at baseline is universal but heterogeneous in patients with relapsed/refractory multiple myeloma.
- High BCMA expression by flow cytometry correlates with better clinical outcomes, including deeper responses and longer time to progression.
- BCMA loss is rare at relapse, but decreased expression is common, with half of paired samples showing downregulation.
- Flow cytometry and immunohistochemistry show poor concordance in categorizing BCMA expression levels.
- Retained BCMA expression at relapse suggests potential for sequencing BCMA-directed therapies.
Macrophage-derived extracellular vesicles in the remodeling of the prostate cancer immune microenvironment and therapeutic resistance - PubMed
5 days ago
- The article discusses the role of macrophage-derived extracellular vesicles in reshaping the prostate cancer immune microenvironment and contributing to therapeutic resistance.
- Keywords include Extracellular vesicle, Immune microenvironment, Prostate cancer, Therapeutic resistance, and Tumor-associated macrophage, indicating the main focus areas.
- No conflicts of interest were declared by the authors, and ethical approvals or consents were noted as not applicable for this study.
- The references provide context through related studies on biomarkers, PET imaging, and immune mechanisms in prostate cancer progression and treatment.
Cardiovascular pharmacotherapy in year in 2025 - PubMed
5 days ago
- Four new drugs were approved: aficamten, etripamil, lerodalcibep, and plozasiran.
- Label expansions occurred for five already approved drugs.
- Results from major randomized clinical trials included both positive and neutral/negative outcomes.
- Andexanet-alfa was withdrawn from the U.S. market due to safety concerns.
- Promising experimental cardiovascular drugs are in ongoing phase 2 and 3 trials.
Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review - PubMed
5 days ago
- Mitochondrial dysfunction is central to age-related macular degeneration (AMD), particularly affecting the retinal pigment epithelium (RPE).
- Dysregulation of mitochondrial dynamics—fission, fusion, biogenesis, and mitophagy—leads to fragmented and dysfunctional mitochondria in AMD.
- Consequences include bioenergetic deficits, oxidative stress, and inflammation, driving AMD pathology.
- Therapeutic strategies targeting mitochondrial pathways, such as antioxidants and dynamic modulators, show promise for intervention.
- Future advances in biomarkers and personalized approaches may address root causes of AMD.
Myricetin stabilizes PINK1 to activate mitophagy and ameliorate metabolic dysfunction-associated steatotic liver disease - PubMed
5 days ago
- Myricetin is a bioactive flavonoid from Abelmoschus manihot that shows therapeutic potential for metabolic dysfunction-associated steatotic liver disease (MASLD) and its progressive form, MASH.
- Myricetin treatment ameliorated hepatic steatosis, inflammation, fibrosis, and insulin resistance in mouse models of MASLD/MASH induced by high-fat or GAN diets.
- Transcriptomic analysis revealed enhanced fatty acid β-oxidation and mitochondrial function after myricetin administration.
- Myricetin directly binds to PINK1, stabilizing it on the outer mitochondrial membrane by inhibiting import through TOM40 and cleavage by PARL protease.
- Stabilized PINK1 activates PINK1/Parkin-dependent mitophagy, restoring mitochondrial integrity and quality.
- Silencing PINK1 abolished myricetin's benefits, confirming the mechanism involving PINK1 stabilization and mitophagy activation.
Zuogui pill ameliorates DNA damage and the senescence-associated secretory phenotype in ovarian stem cells to delay ovarian ageing through activation of SIRT1 - PubMed
5 days ago
- Zuogui Pill (ZGP) delays ovarian aging by enhancing ovarian stem cell (OSC) stemness, increasing follicle count, and raising serum AMH and E2 levels.
- ZGP upregulates SIRT1 to suppress DNA damage (γ-H2AX and CHEK2) and modulate acetylation of Ku70 and p65, reducing p53/p21 expression and SASP.
- The study employs bioinformatics (WGCNA, network pharmacology) and experimental validation in mice and D-gal-induced OSC models to confirm SIRT1-dependent mechanisms.
Gut-derived IL-17A via STAT3/RORγt signaling underlies sleep disruption-induced depression: Targeting effects of Schisandrin B therapy - PubMed
5 days ago
- Sleep disruption induces depression through gut-derived IL-17A signaling via STAT3/RORγt, leading to neuroinflammation.
- Schisandrin B, from Schisandra chinensis, reverses depressive behaviors by restoring gut-brain axis balance and suppressing IL-17A inflammation.
- Clinical and mouse studies show elevated IL-17A and metabolic issues in depression, with Schisandrin B improving gut barrier and neural function.
- Schisandrin B targets MAPK1 and GSK3β, inhibiting STAT3/RORγt, highlighting its potential as a natural immunomodulatory therapy for mood disorders.
Informal caregivers' preferences for self-care support services in caring for community-dwelling older adults with disabilities: A discrete choice experiment - PubMed
5 days ago
- Informal caregivers prioritize self-care support services, especially frequent respite and comprehensive health guidance, over cost considerations.
- A discrete choice experiment with 226 caregivers in Qingdao, China, identified respite service frequency (24.0% relative importance) and health guidance content (21.7%) as the most influential attributes.
- Caregivers' willingness-to-pay was estimated at ¥3132.48 monthly for weekly respite and ¥2827.48 for comprehensive health guidance, showing minimal influence from cost (0.01%).
- Significant preference heterogeneity exists, linked to sociodemographic factors, health status, stress levels, and patient outcomes, highlighting the need for individualized support.
- Community nurses are crucial for assessing caregiver strain, delivering tailored guidance, coordinating services, and ensuring equitable access to enhance caregiver sustainability and care quality.
Gut microbiota and pattern recognition receptors in polycystic ovary syndrome - PubMed
5 days ago
- PCOS is recognized as a disorder of impaired immune-endocrine homeostasis.
- Gut dysbiosis and microbial metabolite imbalance activate pattern recognition receptors (PRRs), forming a PRR-microbiota-reproductive axis.
- Gut-derived signals like LPS and SCFAs modulate TLR, NLR, and RLR pathways, disrupting immune regulation.
- The Reproductive Immune Tolerance Disruption Theory proposes chronic PRR activation shifts reproductive immunity to a low-grade inflammatory state.
- This inflammation promotes hyperandrogenism, anovulation, insulin resistance, and metabolic dysfunction in PCOS.
- Multi-omics studies clarify crosstalk between gut microbial signatures and innate immune signaling.
- Potential therapies include PRR-selective immunomodulation, microbiota-based treatments, and epigenetic metabolic interventions.
- Understanding PRR-driven immunomodulation helps reconcile endocrine, metabolic, and reproductive abnormalities in PCOS.
LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing - PubMed
5 days ago
- LINC00607 is a long non-coding RNA that regulates alternative splicing of the VEGF receptor FLT1 in endothelial cells, influencing angiogenesis.
- Knockout of LINC00607 increases production of soluble FLT1 (sFLT1), a decoy receptor that inhibits VEGF signaling and impairs angiogenesis, which can be reversed with sFLT1-neutralizing antibodies.
- LINC00607 interacts with U2 snRNA and depends on the chromatin remodeler BRG1 to prevent exon 15 inclusion in FLT1, thus reducing sFLT1 formation.
- A splice-blocking morpholino targeting the FLT1 intron14/exon15 junction reduces sFLT1 production and enhances VEGF-A-mediated sprouting by interacting with LINC00607 and U2 snRNA.
- LINC00607 expression is downregulated in preeclampsia and inversely correlates with sFLT1 levels in vascular diseases, suggesting a role in the pathophysiology of conditions like preeclampsia.
Autologous CD19 CAR T-cell therapy for pediatric and adult systemic lupus erythematosus: a phase 1/2 trial - PubMed
5 days ago
- The trial evaluates autologous CD19 CAR T-cell therapy for systemic lupus erythematosus in a phase 1/2 design.
- Primary endpoints focus on dose-limiting toxicity and adverse events in phase 1, and response rates at 3 and 6 months in phase 2.
- Eighteen patients were enrolled, mostly pediatric, with 15 having a SLEDAI-2K score ≥4.
- No dose-limiting toxicities occurred, and the recommended dose for phase 2 was 1×10^6 CAR T cells/kg.
- Adverse events included grade 1 cytokine release syndrome in 72%, neurotoxicity in 17%, and infections in 17%.
- Response rates at month 3 and 6 for patients with SLEDAI-2K ≥4 were 9 out of 15 and 12 out of 15 achieving SRI-S response, with some achieving LLDAS or DORIS remission.
- Median follow-up was 10.2 months, with most responders maintaining response without immunosuppressants, and CAR T cells persisted for a median of 56 days.
An in vivo CRISPR screen unveils promising target genes to improve CAR-T cell efficacy in a solid tumor model - PubMed
5 days ago
- CAR-T cell therapies face limitations, including poor persistence and inefficacy against solid tumors.
- An in vivo CRISPR screen targeting 50 genes identified REGNASE-1, SOCS1, PTPN2, and P16INK4A as top targets to enhance CAR-T cell persistence in a lung tumor model.
- Disruption of genes like MED12, PRDM1, and BATF, previously thought beneficial, was detrimental in this context, indicating context-dependent effects.
- The study underscores the need for context-specific evaluations of genetic modifications to optimize CAR-T therapies for clinical translation.
SARS-CoV-2 directly infects the inner ear and causes hearing dysfunction - PubMed
5 days ago
- SARS-CoV-2 infects inner ear spiral ganglion neurons in mice, leading to hearing dysfunction.
- Spike protein overexpression disrupts stress granule regulation via mTOR inhibition, causing neuronal phase separation and apoptosis.
- Findings suggest an inflammation-independent pathway for COVID-19-related hearing loss.

Hasty Briefsbeta

Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data - PubMed

New insights in multiple sclerosis pathology - PubMed

Prospective real-world experience with risankizumab in difficult-to-treat Crohn's disease: results from the Dutch Initiative on Crohn and Colitis Registry - PubMed

Adverse events after Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System, 2024-2025, United States - PubMed

Integrating network toxicology and experimental validation reveals the immunotoxic effects of acetylcitric acid tributyl ester on systemic lupus erythematosus - PubMed

Molecular pathways driving clarithromycin benefit in community-acquired pneumonia: analysis of the ACCESS randomised trial - PubMed

Maternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions - PubMed

Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy - PubMed

Macrophage-derived extracellular vesicles in the remodeling of the prostate cancer immune microenvironment and therapeutic resistance - PubMed

Cardiovascular pharmacotherapy in year in 2025 - PubMed

Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review - PubMed

Myricetin stabilizes PINK1 to activate mitophagy and ameliorate metabolic dysfunction-associated steatotic liver disease - PubMed

Zuogui pill ameliorates DNA damage and the senescence-associated secretory phenotype in ovarian stem cells to delay ovarian ageing through activation of SIRT1 - PubMed

Gut-derived IL-17A via STAT3/RORγt signaling underlies sleep disruption-induced depression: Targeting effects of Schisandrin B therapy - PubMed

Informal caregivers' preferences for self-care support services in caring for community-dwelling older adults with disabilities: A discrete choice experiment - PubMed

Gut microbiota and pattern recognition receptors in polycystic ovary syndrome - PubMed

LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing - PubMed

Autologous CD19 CAR T-cell therapy for pediatric and adult systemic lupus erythematosus: a phase 1/2 trial - PubMed

An in vivo CRISPR screen unveils promising target genes to improve CAR-T cell efficacy in a solid tumor model - PubMed

SARS-CoV-2 directly infects the inner ear and causes hearing dysfunction - PubMed

Age at Menopause and Trajectories of Multimorbidity Progression to Mortality: A Multi-State Analysis of UK Biobank Data - PubMed

New insights in multiple sclerosis pathology - PubMed

Prospective real-world experience with risankizumab in difficult-to-treat Crohn's disease: results from the Dutch Initiative on Crohn and Colitis Registry - PubMed

Adverse events after Pfizer's Respiratory Syncytial Virus Vaccine in pregnant women in the Vaccine Adverse Event Reporting System, 2024-2025, United States - PubMed

Integrating network toxicology and experimental validation reveals the immunotoxic effects of acetylcitric acid tributyl ester on systemic lupus erythematosus - PubMed

Molecular pathways driving clarithromycin benefit in community-acquired pneumonia: analysis of the ACCESS randomised trial - PubMed

Maternal nutrition as a key determinant of placental and developing blood-brain barrier xenobiotic protective functions - PubMed

Dynamics of BCMA expression in patients with relapsed/refractory multiple myeloma receiving BCMA-directed CAR-T therapy - PubMed

Macrophage-derived extracellular vesicles in the remodeling of the prostate cancer immune microenvironment and therapeutic resistance - PubMed

Cardiovascular pharmacotherapy in year in 2025 - PubMed

Mitochondrial dynamics and their role in the pathogenesis of age-related macular degeneration: A comprehensive review - PubMed

Myricetin stabilizes PINK1 to activate mitophagy and ameliorate metabolic dysfunction-associated steatotic liver disease - PubMed

Zuogui pill ameliorates DNA damage and the senescence-associated secretory phenotype in ovarian stem cells to delay ovarian ageing through activation of SIRT1 - PubMed

Gut-derived IL-17A via STAT3/RORγt signaling underlies sleep disruption-induced depression: Targeting effects of Schisandrin B therapy - PubMed

Informal caregivers' preferences for self-care support services in caring for community-dwelling older adults with disabilities: A discrete choice experiment - PubMed

Gut microbiota and pattern recognition receptors in polycystic ovary syndrome - PubMed

LINC00607 facilitates endothelial VEGF-A receptor FLT1 splicing - PubMed

Autologous CD19 CAR T-cell therapy for pediatric and adult systemic lupus erythematosus: a phase 1/2 trial - PubMed

An in vivo CRISPR screen unveils promising target genes to improve CAR-T cell efficacy in a solid tumor model - PubMed

SARS-CoV-2 directly infects the inner ear and causes hearing dysfunction - PubMed