As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewe...As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewed commitment to ethical and scientific excellence in animal-based research.Throughout 2025,PALAS has continued to strengthen the laboratory animal science community by advancing education,capacity building,policy advocacy,and regional cooperation.These efforts underscore PALAS’vital role in shaping a culture of responsible animal research aligned with international standards.展开更多
Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival a...Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.展开更多
Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, ...Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, but also on the resolution of postischemic immune dysregulation. This study(Chen et al., Prog Biochem Biophys, 2026, 53(3): 697-710. DOI:10.3724/j.pibb.2025.0541) a dvances this emerging paradigm by proposing a therapeutic strategy that integrates lesion-specific delivery with active modulation of the inflammatory microenvironment.展开更多
Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platf...Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).展开更多
Our optic nerves are vulnerable to both traumatic and non-traumatic insults,rendering optic neuropathy a leading cause of permanent and irreversible visual impairment.Optic neuropathies can arise from hereditary[e.g.,...Our optic nerves are vulnerable to both traumatic and non-traumatic insults,rendering optic neuropathy a leading cause of permanent and irreversible visual impairment.Optic neuropathies can arise from hereditary[e.g.,dominant optic atrophy(DOA)and Leber hereditary optic neuropathy(LHON)],ischaemic(e.g.,anterior and posterior ischaemic optic neuropathy),inflammatory(e.g.,optic neuritis),toxic(e.g.,methanol,ethambutol)and nutritional(e.g.,vitamin B12 deficiency),or traumatic conditions.Amongst these,glaucomatous optic neuropathy represents the most prevalent form and constitutes the second leading cause of blindness worldwide,with approximately 10%of patients developing bilateral blindness.Currently,over 76 million people are affected by glaucoma globally-a number predicted to rise to 112 million by 2040.Current treatments primarily focus on lowering intraocular pressure(IOP)through topical medications and surgical interventions.展开更多
Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endo...Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.展开更多
Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggress...Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggressive growth and tendency to spread.Epithelial-mesenchymal transition(EMT)is a central regulatory hub driving tumor cell migration and invasion by enabling changes in cell characteristics.During EMT,epithelial cells gradually take on mesenchymal traits,gaining mobility and spreading mo re easily.Recent multi-omics studies show that many cancer cells exist in a hybrid or partial-EMT state,which lies between the full epithelial and mesenchymal forms.Cells in this state are especially invasive and metastatic,with high plasticity that promotes tumor progression.This review summarizes the role of partial-EMT in OSCC,with a focus on how it alters the tumor microenvironment(TME),promotes invasion and metastasis,and influences cancer stem cells(CSCs).We also highlight the link between partial-EMT and treatment resistance in OSCC.Based on these insights,we discuss therapeutic strategies targeting partial-EMT to improve outcomes.Targeting partial-EMT may offer promising strategies to enhance treatment effectiveness and improve patient survival and quality of life.展开更多
This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to...This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.展开更多
Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular st...Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.展开更多
The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evi...The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.展开更多
Non-O1/non-O139 Vibrio(V.)cholerae(NOVC)has emerged as a potential pathogen in patients with compromised health conditions[1].We report the whole genome sequencing(WGS)of a rare NOVC sepsis isolate(GenBank Accession:G...Non-O1/non-O139 Vibrio(V.)cholerae(NOVC)has emerged as a potential pathogen in patients with compromised health conditions[1].We report the whole genome sequencing(WGS)of a rare NOVC sepsis isolate(GenBank Accession:GCF_051906115.1)from an 89-year-old male admitted to the Intensive Care Unit(ICU)with septic shock(lactate 6.61 mmol/L)digestive illness.展开更多
The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review ar...The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.展开更多
Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability...Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.展开更多
Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferro...Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.展开更多
Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated...Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).展开更多
Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despit...Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despite extensive research,no effective treatment exists,highlighting the need to elucidate mechanisms driving ALS pathogenesis.About 90%of ALS cases are sporadic ALS and lack a clear genetic cause;the remaining 10%are familial ALS,associated with mutations in over 25 genes.The most common mutations are in superoxide dismutase 1(SOD1)and C9ORF72,with rarer variants in FUS,TARDBP,TBK1,and VCP.展开更多
BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in m...BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).展开更多
Radiopharmaceuticals deliver diagnostic or therapeutic radionuclides to disease sites with molecular precision.Over the past five years,clinical adoption has accelerated,led by U.S.Food and Drug Administration approva...Radiopharmaceuticals deliver diagnostic or therapeutic radionuclides to disease sites with molecular precision.Over the past five years,clinical adoption has accelerated,led by U.S.Food and Drug Administration approvals of 177Lu-DOTA-TATE and 177Lu-PSMA-617 and their complementary Positron Emission Tomography agents(68Ga-DOTA-TATE,68Ga-PSMA-11),which have established radiotheranostics as a pillar of oncology care.The new generation of agents couples optimized radionuclides(β-,α,and Auger emitters)to antibodies,peptides,and small-molecule vectors that improve tumor uptake,residence time,and clearance profiles,thereby enhancing efficacy and safety.Beyond neuroendocrine tumors and prostate cancer,radiotheranostic strategies are advancing for diverse malignancies by exploiting tumor-specific antigens,overexpressed receptors,and intracellular targets.Notably,α-emitters such as 225Ac and 211At—owing to high linear energy transfer and short path length—show potent cytotoxicity with limited off-target injury,while emergingβ/Auger emitters like 161Tb may surpass 177Lu in microdosimetric effectiveness.Concurrent innovations in patient selection and response prediction leverage diagnostic radiopharmaceuticals for image-guided stratification,individualized dosimetry,and adaptive treatment planning,supporting the broader paradigm of precision medicine.Although oncology remains the primary focus,applications are expanding to neurodegeneration,cardiovascular disease,and inflammatory conditions.This review synthesizes technological and clinical progress from 2021-2025,spanning FDA-approved and late-stage investigational agents;mechanisms of radiopharmaceutical-induced cell death;dosimetry methodologies;trial landscapes for expanding indications;and translational challenges,including supply chains,chelation chemistry,and toxicity management.Accordingly,this review focuses on the latest radiopharmaceutical diagnostic and therapeutic technologies,integrating advances in radionuclide platforms,targeting vectors,dosimetry,and clinical trial data from 2021-2025 to guide future development and clinical implementation of precision radiotheranostics.展开更多
Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinoce...Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinocerebellar ataxia type 2(SCA2)and amyotrophic lateral sclerosis(ALS),ataxin-2 functions span far beyond its pathogenic properties in the disease context(Figure 1).In fact,it has a wide range of biological functions that include RNA metabolism,translation regulation,stress response,endocytosis,calcium signaling,and the control of circadian rhythm.In this perspective,we highlight the main roles of ataxin-2 protein,which are described in detail in Costa et al.(2024).展开更多
The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore functio...The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).展开更多
文摘As the Philippines celebrated the 2nd Asia Laboratory Animal Day(ALAD)last November 29,2025,the Philippine Association for Laboratory Animal Sciences(PALAS)reflected on a year marked by growth,collaboration,and renewed commitment to ethical and scientific excellence in animal-based research.Throughout 2025,PALAS has continued to strengthen the laboratory animal science community by advancing education,capacity building,policy advocacy,and regional cooperation.These efforts underscore PALAS’vital role in shaping a culture of responsible animal research aligned with international standards.
基金supported by the National Research Foundation of Korea,Nos.2021R1A2C2006110,2021M3E5D9021364,2019R1A5A2026045(to BGK)the Korea Initiative for Fostering University of Research and Innovation(KIURI)Program of the NRF funded by the MSIT(to HK),No.NRF2021M3H1A104892211(to HSK)。
文摘Spinal cord injury results in permanent loss of neurological functions due to severance of neural networks.Transplantation of neural stem cells holds promise to repair disrupted connections.Yet,ensuring the survival and integration of neural stem cells into the host neural circuit remains a formidable challenge.Here,we investigated whether modifying the intrinsic properties of neural stem cells could enhance their integration post-transplantation.We focused on phosphatase and tensin homolog(PTEN),a well-characterized tumor suppressor known to critically regulate neuronal survival and axonal regeneration.By deleting Pten in mouse neural stem cells,we observed increased neurite outgrowth and enhanced resistance to neurotoxic environments in culture.Upon transplantation into injured spinal cords,Pten-deficient neural stem cells exhibited higher survival and more extensive rostrocaudal distribution.To examine the potential influence of partial PTEN suppression,rat neural stem cells were treated with short hairpin RNA targeting PTEN,and the PTEN knockdown resulted in significant improvements in neurite growth,survival,and neurosphere motility in vitro.Transplantation of sh PTEN-treated neural stem cells into the injured spinal cord also led to an increase in graft survival and migration to an extent similar to that of complete deletion.Moreover,PTEN suppression facilitated neurite elongation from NSC-derived neurons migrating from the lesion epicenter.These findings suggest that modifying intrinsic signaling pathways,such as PTEN,within neural stem cells could bolster their therapeutic efficacy,offering potential avenues for future regenerative strategies for spinal cord injury.
文摘Ischemic stroke therapy has long been dominated by strategies aimed at restoring cerebral blood flow. Yet, accumulating evidence suggests that neuronal survival and functional recovery depend not only on reperfusion, but also on the resolution of postischemic immune dysregulation. This study(Chen et al., Prog Biochem Biophys, 2026, 53(3): 697-710. DOI:10.3724/j.pibb.2025.0541) a dvances this emerging paradigm by proposing a therapeutic strategy that integrates lesion-specific delivery with active modulation of the inflammatory microenvironment.
基金supported by the Hunan Natural Science Foundation(2023JJ20022).
文摘Tumor immunotherapy has been recognized by Science as the most promising therapeutic approach for tumor eradication,with engineered bacteria emerging as a particularly promising modality.As a novel drug delivery platform,the engineered bacterial therapeutics demonstrate exceptional targeting precision and favorable safety profiles.Through attenuation and programmable control strategies,these systems enable highly specific drug delivery,showing significant therapeutic potential in oncology and inflammatory bowel disease(IBD).
基金Fight for Sight/Glaucoma UK(RESSGA2510)the Royal Society Project Grant(RG\R1\251126)Rosetrees Trust/Stoneygate Trust(Seedcorn2024\100044)awarded to NPBA.
文摘Our optic nerves are vulnerable to both traumatic and non-traumatic insults,rendering optic neuropathy a leading cause of permanent and irreversible visual impairment.Optic neuropathies can arise from hereditary[e.g.,dominant optic atrophy(DOA)and Leber hereditary optic neuropathy(LHON)],ischaemic(e.g.,anterior and posterior ischaemic optic neuropathy),inflammatory(e.g.,optic neuritis),toxic(e.g.,methanol,ethambutol)and nutritional(e.g.,vitamin B12 deficiency),or traumatic conditions.Amongst these,glaucomatous optic neuropathy represents the most prevalent form and constitutes the second leading cause of blindness worldwide,with approximately 10%of patients developing bilateral blindness.Currently,over 76 million people are affected by glaucoma globally-a number predicted to rise to 112 million by 2040.Current treatments primarily focus on lowering intraocular pressure(IOP)through topical medications and surgical interventions.
文摘Background:Minimally invasive distal pancreatectomy(MIDP)is increasingly being used,although its oncologic safety for pancreatic ductal adenocarcinoma(PDAC)remains controversial.In Japan,MIDP for PDAC has limited endorsement due to insufficient data.This study aimed to compare the perioperative and long-term outcomes of open distal pancreatectomy(ODP)and MIDP for PDAC.Methods:We retrospectively analyzed patients with resectable pancreatic body and tail cancer treated with ODP or MIDP(laparoscopic or robotic)between January 2007 and July 2022.The surgical procedures(ODP and MIDP)were compared and the patient characteristics,perioperative outcomes,and long-term outcomes were analyzed.We also compared the outcomes of patients with neoadjuvant chemotherapy(NAC)and without NAC.Results:A total of 72 distal pancreatectomies were performed(37 ODPs and 35 MIDPs).In the upfront group,MIDP resulted in significantly less blood loss than ODP(P<0.01),despite similar operative time.There was no statistically significant difference in the 2-year recurrence-free survival(RFS)rates between ODP and MIDP(39.7%vs.57.8%,P=0.60)or in the overall survival(OS)rates(66.7%vs.74.1%,P=0.43).Similarly,in the NAC group,MIDP resulted in significantly less blood loss than ODP(P=0.01);ODP and MIDP had similar 2-year RFS rates(41.7%and 60.0%,P=0.75)and OS rates(50.0%and 70.0%,P=0.36).The interval from surgery to adjuvant chemotherapy initiation did not significantly differ between the ODP and MIDP subgroups in both the upfront group(P=0.13)and the NAC group(P=0.14).The incidence of recurrence was 64.8%for ODP and 42.8%for MIDP(P=0.06).Both procedures showed similar distributions of local and distant recurrence.Conclusions:MIDP caused less blood loss and had similar oncologic safety compared with ODP.MIDP could become a feasible,minimally invasive option with sufficient oncologic safety for pancreatic body and tail cancers.
基金funded by JSPS KAKENHI to Y.K.(22K19629,22H03288,and 21KK0162)JSPS Program for Forming Japan's Peak Research Universities:J-PEAKS(JPJS00420240022)to Y.K.JST SPRING,Grant Number JPMJSP2113 to C.W.and C.S.
文摘Oral squamous cell carcinoma(OSCC)is a prevalent malignancy with high morbidity and mortality.Globally,about 400000 people are affected,often with a poor quality of life.Its high mortality is mainly due to its aggressive growth and tendency to spread.Epithelial-mesenchymal transition(EMT)is a central regulatory hub driving tumor cell migration and invasion by enabling changes in cell characteristics.During EMT,epithelial cells gradually take on mesenchymal traits,gaining mobility and spreading mo re easily.Recent multi-omics studies show that many cancer cells exist in a hybrid or partial-EMT state,which lies between the full epithelial and mesenchymal forms.Cells in this state are especially invasive and metastatic,with high plasticity that promotes tumor progression.This review summarizes the role of partial-EMT in OSCC,with a focus on how it alters the tumor microenvironment(TME),promotes invasion and metastasis,and influences cancer stem cells(CSCs).We also highlight the link between partial-EMT and treatment resistance in OSCC.Based on these insights,we discuss therapeutic strategies targeting partial-EMT to improve outcomes.Targeting partial-EMT may offer promising strategies to enhance treatment effectiveness and improve patient survival and quality of life.
基金Supported by Japan Society for the Promotion of Science,No.24K11935.
文摘This review comprehensively summarized the potential of artificial intelligence(AI)in the management of esophageal cancer.It highlighted the significance of AI-assisted endoscopy in Japan where endoscopy is central to both screening and diagnosis.For the clinical adaptation of AI,several challenges remain for its effective translation.The establishment of high-quality clinical databases,such as the National Clinical Database and Japan Endoscopy Database in Japan,which covers almost all cases of esophageal cancer,is essential for validating multimodal AI models.This requires rigorous external validation using diverse datasets,including those from different endoscope manufacturers and image qualities.Furthermore,endoscopists’skills significantly affect diagnostic accuracy,suggesting that AI should serve as a supportive tool rather than a replacement.Addressing these challenges,along with country-specific legal and ethical considerations,will facilitate the successful integration of multimodal AI into the management of esophageal cancer,particularly in endoscopic diagnosis,and contribute to improved patient outcomes.Although this review focused on Japan as a case study,the challenges and solutions described are broadly applicable to other high-incidence regions.
基金supported by the National Italian Research Council(CNR)“Progetto DSB.AD007.305.001”to Monica Rinaldi。
文摘Hepatitis C virus(HCV)and hepatitis B virus(HBV)infections are increasingly recognized as significant etiological factors in the pathogenesis of B-cell non-Hodgkin’s lymphomas(B-NHLs).Epidemiological and molecular studies have demonstrated a consistent association between chronic viral infection and B-NHLs.Multiple pathogenic mechanisms have been implicated in lymphomagenesis,both direct and indirect,including chronic antigenic stimulation,direct infection of B cells,and viral protein-mediated oncogenic signaling,It is likely that a combination of several pathogenic conditions is required to eventually lead to the development of lymphoma.The prevalence of B-cell lymphomas among individuals with chronic HCV or HBV infection presents a complex pathogenetic scenario,given the tumor heterogeneity and variable clinical behavior,and poses therapeutic challenges,due to the partial efficacy of current treatment options.The advent of direct-acting antivirals(DAAs)for HCV and high-genetic barrier nucleos(t)ide analogues(NAs)for HBV has improved patient outcomes.In indolent HCV-associated B-NHLs,antiviral therapy with DAAs alone often achieves sustained virologic response and may lead to lymphoma regression.Conversely,aggressive subtypes like diffuse large B-cell lymphomas require combination treatment with immunochemotherapy.In the setting of HBV-associated lymphomas,antiviral prophylaxis with potent NAs(e.g.,entecavir or tenofovir)is essential to prevent HBV reactivation during rituximab-containing chemotherapy regimen.The integration of antiviral and anticancer therapies has been shown to enhance survival outcomes while mitigating hepatic toxicity.A comprehensive understanding of the biological interplay between chronic viral infection and B-cell transformation is critical for optimizing diagnostic and therapeutic strategies.Aim of this viewpoint is to provide evidence that early viral detection and prompt management remain the most effective strategies to improve survival rates and to reduce treatment-related morbidity in these patients.
基金supported by grants from NIH T32(DK007260,to WC)the Steno North American Fellowship awarded by the Novo Nordisk Foundation(NNF23OC0087108,to WC).
文摘The shared links between Alzheimer’s disease and type 2 diabetes mellitus:Alzheimer’s disease(AD)and type 2 diabetes mellitus(T2DM)are two prevalent conditions that come with substantial daily struggles.Emerging evidence highlights that these diseases share similar pathophysiological features,including insulin resistance and chronic inflammation,which contribute to their rapid progression(Chen et al.,2022).Insulin resistance,a hallmark of T2DM,has been suggested to exacerbate neurodegeneration in AD.Similarly,chronic low-grade inflammation in T2DM parallels with neuroinflammation,which is observed in AD,suggesting overlapping pathophysiological mechanisms in T2DM and AD.
文摘Non-O1/non-O139 Vibrio(V.)cholerae(NOVC)has emerged as a potential pathogen in patients with compromised health conditions[1].We report the whole genome sequencing(WGS)of a rare NOVC sepsis isolate(GenBank Accession:GCF_051906115.1)from an 89-year-old male admitted to the Intensive Care Unit(ICU)with septic shock(lactate 6.61 mmol/L)digestive illness.
文摘The addition of sarcomeres in series(sarcomerogenesis)in skeletal muscle has increasingly fascinated exercise scientists in recent years due to its potential to positively impact performance.1,2 In their new review article,Triggering sarcomerogenesis:Examining key stimuli and the role attributed to eccentric training—Historical,systematic,and meta-analytic review,Blazevich et al.3 provide a commendable overview of the history behind this area of research from the 1600s to present.
基金supported by the National Natural Science Foundation of China(82373277).
文摘Delivery carriers serve as a highly efficient approach for precision nutrition and medicine;however,artificial delivery carriers are prone to triggering the immune response and have the disadvantages of poor stability and low bioavailability.Extracellular vesicles(EVs),nucleus-free biological particles composed of phospholipid bilayers secreted by living cells,are a new generation of targeted delivery carriers.In recent years,an increasing number of species have been reported to contain EVs.Among them,food-derived extracellular vesicles(FDEVs)show outstanding comprehensive properties.FDEVs are considered to have great application potential due to their wide range of sources,high yields,absence of human pathogenic pathogens,and ethical concerns.In this review,the preparation,nomenclature,physicochemical characteristics,and preservation methods of FDEVs are discussed,as well as their potential protein markers,bioactivities,and applications as novel targeted delivery carriers of FDEVs from animals,plants,and microorganisms.We also summarized the adverse consequences of FDEVs in current studies,and put forward the problems and challenges in the process of FDEVs research and commercialization.In short,the importance of FDEVs has been highlighted,and FDEVs have good application prospects as a new class of targeted delivery carriers.The current problems should be paid attention to and actively solved.
基金supported by Regione Autonoma della Sardegna,pursuant to Regional Law 07 August 2007,n.7“Promotion of Scientific Research and Technological Innovation in Sardinia—UGOV Project RAS_CRP2023 CARRULilt Nazionale—5 per mille Program for the year 2022,LILT 2023 scientific-health research call,Number:LILT—Protocol number 2024U0001294 of 29.03.2024。
文摘Background:An increasing number of studies have shown that ferroptosis is related to the initiation and development of small cell lung cancer(SCLC).The systematic review aimed to summarize the characteristics of ferroptosis from its pathogenetic role to translational therapeutic implications in SCLC.Methods:This systematic review,registered in PROSPERO(CRD420251090058),followed PRISMA 2020 guidelines.Comprehensive research of PubMed,Scopus,and Web of Science was performed for studies published between January 2010 and July 2025 investigating ferroptosis mechanisms,genetic or pharmacological modulation,or molecular profiling in SCLC.Two reviewers independently performed data extraction and quality assessment.Results:Nineteen preclinical studies met the inclusion criteria.Key regulators included solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),ferroptosis suppressor protein 1(FSP1),and acyl-CoA synthetase long chain family member 4(ACSL4).The molecular subtypes of SCLC,achaete-scute homolog 1(ASCL1),neuronal differentiation 1(NEUROD1),POU class 2 homeobox 3(POU2F3),and Yes1 associated transcriptional regulator(YAP1)exhibit differential ferroptosis gene expressions,influencing therapeutic responsiveness.Non-neuroendocrine subtypes are more ferroptosis-prone,whereas neuroendocrine variants display enhanced antioxidant defenses.Ferroptosis induction also promotes immune activation through stimulator of interferon genes(STING)-mediated CD8+T-cell recruitment.Conclusions:Ferroptosis constitutes a promising therapeutic axis in SCLC.Integrating ferroptosis biomarkers into molecular stratification frameworks could refine patient selection and support precision oncology strategies,warranting further translational and clinical validation.
文摘Obese individuals who subsequently sustain a traumatic brain injury(TBI)exhibit worsened outcomes including longer periods of rehabilitation(Eagle et al.,2023).In obese individuals,prolonged symptomology is associated with increased levels of circulato ry pro-inflammatory marke rs up to 1 year postTBI(Eagle et al.,2023).
文摘Amyotrophic lateral sclerosis(ALS)is a progressive neurodegenerative disease marked by motor neuron(MN)degeneration,neuromuscular junction disruption,and muscle atrophy,ultimately leading to paralysis and death.Despite extensive research,no effective treatment exists,highlighting the need to elucidate mechanisms driving ALS pathogenesis.About 90%of ALS cases are sporadic ALS and lack a clear genetic cause;the remaining 10%are familial ALS,associated with mutations in over 25 genes.The most common mutations are in superoxide dismutase 1(SOD1)and C9ORF72,with rarer variants in FUS,TARDBP,TBK1,and VCP.
基金supported by the award W81XWH1910309 (to HF) from the Department of Defensethe award R01-AG075092-01 (to HF)+2 种基金the award RF1AG063521 from the National Institute of Aging at the National Institutes of Healththe Neurological Research Institute Seed grant (to HF) from The Ohio State Universitythe Summer Undergraduate Research Fellowship (to NS) from The Ohio State University Chronic Brain Injury Discovery Theme
文摘BCL2-associated anthanogene 3 facilitates the clearance of tau protein aggregates:BCL2-associated anthanogene 3(BAG3)is a ubiquitously expressed and highly conserved multi-functional co-chaperone protein involved in many biological processes that supports cellular homeostasis,including the inhibition of apoptosis by preventing mitochondrial BAX localization(Lin et al.,2022)and the promotion of the degradation of hyperphosphorylated tau aggregates by its interactions with SQSTM1(p62)(Hamano and Mutoh,2022).
基金supported by the NRF-2021R1C1 C1009541,2022R1FA1063012.
文摘Radiopharmaceuticals deliver diagnostic or therapeutic radionuclides to disease sites with molecular precision.Over the past five years,clinical adoption has accelerated,led by U.S.Food and Drug Administration approvals of 177Lu-DOTA-TATE and 177Lu-PSMA-617 and their complementary Positron Emission Tomography agents(68Ga-DOTA-TATE,68Ga-PSMA-11),which have established radiotheranostics as a pillar of oncology care.The new generation of agents couples optimized radionuclides(β-,α,and Auger emitters)to antibodies,peptides,and small-molecule vectors that improve tumor uptake,residence time,and clearance profiles,thereby enhancing efficacy and safety.Beyond neuroendocrine tumors and prostate cancer,radiotheranostic strategies are advancing for diverse malignancies by exploiting tumor-specific antigens,overexpressed receptors,and intracellular targets.Notably,α-emitters such as 225Ac and 211At—owing to high linear energy transfer and short path length—show potent cytotoxicity with limited off-target injury,while emergingβ/Auger emitters like 161Tb may surpass 177Lu in microdosimetric effectiveness.Concurrent innovations in patient selection and response prediction leverage diagnostic radiopharmaceuticals for image-guided stratification,individualized dosimetry,and adaptive treatment planning,supporting the broader paradigm of precision medicine.Although oncology remains the primary focus,applications are expanding to neurodegeneration,cardiovascular disease,and inflammatory conditions.This review synthesizes technological and clinical progress from 2021-2025,spanning FDA-approved and late-stage investigational agents;mechanisms of radiopharmaceutical-induced cell death;dosimetry methodologies;trial landscapes for expanding indications;and translational challenges,including supply chains,chelation chemistry,and toxicity management.Accordingly,this review focuses on the latest radiopharmaceutical diagnostic and therapeutic technologies,integrating advances in radionuclide platforms,targeting vectors,dosimetry,and clinical trial data from 2021-2025 to guide future development and clinical implementation of precision radiotheranostics.
基金Cure CSB ProjectViljem Julijan Association for Children with Rare Diseases(Slovenia)+1 种基金Algarve Biomedical Center Research Institute(ABC-Ri)AC received a PhD fellowship from the Portuguese Science and Technology Foundation(FCT)#2020.07892.BD.
文摘Ataxin-2 is a 140 kDa cytoplasmic multifunctional protein that plays fundamental roles in diverse cellular mechanisms(Costa et al.,2024).Although widely studied in the context of the neurodegenerative diseases spinocerebellar ataxia type 2(SCA2)and amyotrophic lateral sclerosis(ALS),ataxin-2 functions span far beyond its pathogenic properties in the disease context(Figure 1).In fact,it has a wide range of biological functions that include RNA metabolism,translation regulation,stress response,endocytosis,calcium signaling,and the control of circadian rhythm.In this perspective,we highlight the main roles of ataxin-2 protein,which are described in detail in Costa et al.(2024).
基金supported by the University of Padua(to MR)by the project“RIPANE”of the Italian Ministry of Defense(to CM)by Cariparo Foundation(to CM)。
文摘The neuromuscular junction and its proregenerative niche:The mammalian peripheral nervous system,unlike the central nervous system,has preserved throughout evolution the ability to regenerate and fully restore function.Key factors for effective nerve regeneration include a supportive neuronal environment and a coordinated tissue response(Brosius Lutz and Barres,2014).
