BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality...BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality.Its adaptogenic and anti-inflammatory properties promote hormonal balance,physical function,and sexual health,supporting its potential benefits for menopausal health.AIM To investigate Physta®’s role in improving menopausal quality of life,mood states,and overall safety profile compared with placebo.METHODS In this 12-week,randomized,double-blind,placebo-controlled trial,138 females aged 40-55 with menopausal symptoms were randomly assigned to receive Physta®50 mg,Physta®100 mg,or placebo.MENQOL and POMS were assessed at baseline,week 6,and week 12.Safety outcomes were evaluated through biochemical tests,vital signs,and female reproductive hormonal profile.RESULTS Physta®100 mg significantly reduced total MENQOL scores by 33.9%from baseline to week 12(P=0.049)with notable improvements in the physical(-36.4%,P=0.046)and sexual(-36.3%,P=0.043)domains.Total mood disturbance also declined more in the Physta®100 mg group(-38.6%)compared with placebo(-30.1%),although not statistically significant.No significant changes were observed in the vital signs and biochemical parameters,indicating the safety and tolerability of Physta®.No significant alterations were found in the female reproductive hormone profile,supporting its hormonal neutrality.CONCLUSION Physta®100 mg improved menopausal quality of life and mood without adverse effects,supporting its potential as a safe herbal therapy.Further studies with higher doses and longer durations are needed.展开更多
AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was deter...AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.展开更多
Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-asso...Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.展开更多
The complex and variable nature of traumatic spinal cord inju- ry （SCI） presents a unique challenge for translational research. SCI is not bound by any demographic nor is it limited to specific injury biomechanics.
Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types,only a subset of patients shows meaningful clinical responses.In particular,advanced prosta...Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types,only a subset of patients shows meaningful clinical responses.In particular,advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy.This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer.Therefore,it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment.Here,we review recent findings that reveal the roles of the genetic alterations,androgen receptor signaling,cancer cell plasticity,and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance.Based on preclinical and clinical observations,a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.展开更多
Selective vulnerability of excitatory neurons in Alzheimer’s disease(AD):AD is the most common form of dementia;however,the pathogenesis of AD is largely unknown.One of the characteristic features of AD is the format...Selective vulnerability of excitatory neurons in Alzheimer’s disease(AD):AD is the most common form of dementia;however,the pathogenesis of AD is largely unknown.One of the characteristic features of AD is the formation of intracellular neurofibrillary tangles(NFTs).NFTs are abnormal accumulates of misfolded tau protein,which may eventually cause neuronal death and neurodegeneration(Jack et al.,2018).In the early stages of AD progression,not all neurons are equally vulnerable to tau aggregates.Previous studies have shown that large pyramidal neurons in the entorhinal cortex(EC)are specifically vulnerable to pathological tau accumulation(Fu et al.,2017).This selective vulnerability of excitatory neurons to tau pathology is one of the fundamental questions needed to be answered in AD research.展开更多
This study was conducted to observe the genotoxic effects of aqueous, methanol, hexane and dichloromethane extracts of “belacan” (shrimp paste) taken from three local districts in Melaka, Malaysia (Kelemak, Batang T...This study was conducted to observe the genotoxic effects of aqueous, methanol, hexane and dichloromethane extracts of “belacan” (shrimp paste) taken from three local districts in Melaka, Malaysia (Kelemak, Batang Tiga & Pantai Puteri). The umu test which was used as the screening test was conducted with and without the presence of metabolic activation system. Without the presence of metabolic activation system, aqueous extracts from Kelemak showed mutagenicity activity at 5 mg/ml with IR (Induction Rate) = 1.52 ± 0.57 and the methanol extracts showed mutagenic activities at 0.625 mg/ml and 5 mg/ml, which the IR was the highest at 5 mg/ml (2.08 ± 0.09). On the other hand, samples from Batang Tiga, Melaka showed mutagenic effects at all five concentrations for the dichloromethane extract, with IR = 2.09 ± 0.64 as the highest value at 1.25 mg/ml. Methanol extracts also showed positive results at 1.25 mg/ml and 2.5 mg/ml with IR = 1.70 ± 0.33 and IR = 2.12 ± 0.51 respectively, and aqueous extract at 0.625 mg/ml with IR = 1.54 ± 0.48 and 5 mg/ml with IR = 1.74 ± 0.50. There was a significant difference of the mean values of IR between the four different types of “belacan” extracts from Batang Tiga (p < 0.05). All four “belacan” extracts from Pantai Puteri, Melaka did not show any mutagenic effect. With the presence of metabolic activation system, there was no mutagenic effect observed in all four extracts from the three districts. Further study to analyze the contents in the food samples should be done in the future to determine the possible contents in the food samples that might be responsible for the mutagenic activities.展开更多
The androgen receptor(AR)plays a critical role in the development and progression of prostate cancer by regulating key cellular pro-cesses such as cell proliferation and apoptosis.Although traditional AR-targeted ther...The androgen receptor(AR)plays a critical role in the development and progression of prostate cancer by regulating key cellular pro-cesses such as cell proliferation and apoptosis.Although traditional AR-targeted therapies have shown initial success,acquired resis-tance remains a significant clinical challenge,often driven by AR alterations and somatic gene mutations associated with homologous recombination deficiency(HRD).Approximately 20%of advanced prostate cancer cases exhibit HRD,resulting in substantial genomic instability and complicating treatment.Fortunately,Food and Drug Administration–approved poly(ADP-ribose)polymerase inhibitors,in-cluding olaparib and rucaparib,exploit synthetic lethality to target prostate cancer with HRD,and additional drugs targeting DNA dam-age response(DDR)proteins are under development.Emerging evidence suggests that AR activity enhances DDR gene expression,with multiple DDR proteins localized near androgen-regulated regions,highlighting a close interaction between AR and DDR pathways.Consequently,recent preclinical and clinical studies have investigated combining AR-targeted therapies with treatments that induce DNA damage,such as radiation therapy,or inhibit DNA repair mechanisms.This review discusses AR's role in cellular processes,the interplay between AR and DDR,and recent advances in prostate cancer treatment strategies.展开更多
The liver is pivotal in protein synthesis,glucose and lipid metabolism,and detoxification.However,the liver is susceptible to both acute and chronic disorders,with chronic conditions being fatal.Chronic liver diseases...The liver is pivotal in protein synthesis,glucose and lipid metabolism,and detoxification.However,the liver is susceptible to both acute and chronic disorders,with chronic conditions being fatal.Chronic liver diseases(CLDs),such as liver fibrosis,which usually represents the early manifestation of cirrhosis,primarily result from hepatitis B and C viruses infections,metabolic disorders,alcohol abuse,immunemediated attacks,and cholestatic injury.The progression of liver fibrosis contributes to the development of cirrhosis,which can further lead to hepatocellular carcinoma,portal hypertension,hepatic decompensation,and hepatic encephalopathy.The extracellular matrix deposition over time leading the hepatocyte necrosis(cirrhosis)is the main structural feature of CLDs and may cause hepatic failure.Certain conditions,such as hepatitis and autoimmune diseases,may promote the rapid deterioration of liver function.Acute and chronic liver failure causes may vary,with early referral for liver transplantation improving the chance of recovery.The healthcare system need improvements to manage patients with non-alcoholic fatty liver disease and alcoholic fatty liver disease,as they have the potential to progress to cirrhosis.Both conditions involve the release of reactive oxygen species and damage-associated molecular patterns from cytokines,hepatic stellate cells,and hepatocyte autophagy,leading to prolonged inflammation.While various medications target fibrosis and liver damage,nanoparticle-based drug delivery systems offer additional promise by promoting faster liver regeneration.This review provides a comprehensive overview of the potential of nanoparticle systems as a future therapeutic approach for treating liver disorders.展开更多
Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevanc...Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevance in the bloodstream remain unexplored.Given that STAT3-inducing cytokines,such as interleukin-6(IL-6),are often elevated in the bloodstream of various cancer patients[2,3],we aimed to investigate basal STAT3 activation in blood by developing a methodology to assess ex vivo phosphorylation of STAT3(pSTAT3ex vivo)in circulating immune cells.展开更多
Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming gro...Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.Methods:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and HCC.Multiple omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis.The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice.Results:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive correlations.Stimulation of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1.Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 levels.LGALS3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton.The released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback loop.LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis.Moreover,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1.Conclusion:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.展开更多
The ovarian tumor microenvironment plays a critical yet is poorly understood role in the regulation of cancer cell behaviors including proliferation,migration,and response to chemotherapy treatments.Ovarian cancer is ...The ovarian tumor microenvironment plays a critical yet is poorly understood role in the regulation of cancer cell behaviors including proliferation,migration,and response to chemotherapy treatments.Ovarian cancer is the deadliest gynecological cancer,due to diagnosis at late stages of the disease and increased resistance to chemotherapies for recurrent disease.Understanding how the tumor microenvironment(TME)interacts with biomechanical forces to drive changes to ovarian cancer cell behaviors could elucidate novel treatment strategies for this patient population.Additionally,limitations in current preclinical models of the ovarian TME do not permit investigation of crosstalk between signaling pathways and mechanical forces.Our study focused on uncovering how strains and hyaluronic acid(HA)interact to signal through the CD44 receptor to alter ovarian cancer cell growth,migration,and response to a commonly used chemotherapy,paclitaxel.Using an advanced 3D in vitro model,we were able to identify how interactions of strain and HA as in the TME synergistically drive enhanced proliferation and migration in an ovarian tumor model line,while decreasing response to paclitaxel treatment.This study demonstrates the importance of elucidating how the mechanical forces present in the ovarian TME drive disease progression and response to treatment.展开更多
The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and transporters.Several protein isoforms of PXR exist,and they have differential transcr...The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and transporters.Several protein isoforms of PXR exist,and they have differential transcriptional activity upon target genes; transcript variants 3(PXR3) and 4(PXR4) do not induce target gene expression,whereas transcript variants 1(PXR1) and 2(PXR2) respond to agonist by activating target gene expression.PXR protein variants also display differences in protein–protein interactions; PXR1 interacts with p53,whereas PXR3 does not.Furthermore,the transcript variants of PXR that encode these protein isoforms are differentially regulated by methylation and deletions in the respective promoters of the variants,and their expression differs in various human cancers and also in cancerous tissue compared to adjacent normal tissues.PXR1 and PXR4 m RNA are downregulated by methylation in cancerous tissue and have divergent effects on cellular proliferation when ectopically overexpressed.Additional detailed and comparative mechanistic studies are required to predict the effect of PXR transcript variant expression on carcinogenesis,therapeutic response,and the development of toxicity.展开更多
Cytochrome P450(CYP)enzymes function to catalyze a wide range of reactions,many of which are critically important for drug response.Members of the human cytochrome P4503A(CYP3A)family are particularly important in dru...Cytochrome P450(CYP)enzymes function to catalyze a wide range of reactions,many of which are critically important for drug response.Members of the human cytochrome P4503A(CYP3A)family are particularly important in drug clearance,and they collectively metabolize more than half of all currently prescribed medications.The ability of these enzymes to bind a large and structurally diverse set of compounds increases the chances of their modulating or facilitating drug metabolism in unfavorable ways.Emerging evidence suggests that individual enzymes in the CYP3A family play discrete and important roles in catalysis and disease progression.Here we review the similarities and differences among CYP3A enzymes with regard to substrate recognition,metabolism,modulation by small molecules,and biological consequence,highlighting some of those with clinical significance.We also present structural perspectives to further characterize the basis of these comparisons.展开更多
Engineered functional neural interfaces （fNIs） serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimula...Engineered functional neural interfaces （fNIs） serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.展开更多
Objective:Chronic rhinosinusitis(CRS)involves inflammation of the nasal and para-nasal mucosa.Due to its heterogeneous nature,unknown pathogenesis,and high recurrence rate,effective treatment is difficult.Nasal cytolo...Objective:Chronic rhinosinusitis(CRS)involves inflammation of the nasal and para-nasal mucosa.Due to its heterogeneous nature,unknown pathogenesis,and high recurrence rate,effective treatment is difficult.Nasal cytology is presently not a part of the routine diagnosis or treatment decision for CRS.Data sources:A literature search was performed for published papers in English between January 1990 and June 2019 using MEDLINE.Study sdection:Terms used were chronic rhinosinusids,eosinophils,etiology,immunopathology,inflammation,mast cells,nasal cytology,polyps,and treatment.Both reviews and original articles were collected and studied.Results:There is no standard nasal fluid,mucus sampling,or staining techniques for identifying inflammatory cell types.Results were divergent from different countries.Moreover,the main focus of these papers on the cells in nasal washings was eosinophils,with infrequent mentioning of other cell types that may imply different etiology and pathology.The heterogeneous cell profile of CRS and the role of mast cells have been unappreciated due to the lack of specific immunohistochemical technique or study of its unique mediators.Conclusions:Nasal cytology could help distinguish the type and the activation state of inflammatory cells.Thus it can help in providing a clearer picture of CRS pathogenesis,identifying different patient groups,and developing effective treatments.展开更多
DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli,including exposure to drugs of abus...DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli,including exposure to drugs of abuse.Indeed,the medial prefrontal cortex(mPFC)projections to the nucleus accumbens(NAc)are critically important for reinstated cocaine-seeking in a rodent model of cocaine relapse.This circuitry undergoes several epigenetic modifications following cocaine exposure,including changes in DNA methylation that are associated with drug-seeking behavior.We have previously shown that methyl supplementation via L-Methionine(MET)administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos,suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement.In the current study,male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC,optical fibers were surgically implanted into the NAc,and the rats were given injections of MET daily.Rats underwent acquisition of cocaine self-administration(0.75 mg/kg/infusion,2-h sessions)followed by extinction training in the absence of drug-paired cues.Two reinstatement tests were conducted:cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-NAc projections.There were no group differences before the cocaine-primed reinstatement session,and all groups showed robust cue-induced reinstatement.Both rats treated with MET and rats that received mPFC-to-NAc inhibition showed an abolishment of cocaine-primed reinstatement,suggesting that systemic methyl supplementation may act through this critical circuity.展开更多
Esophageal adenocarcinoma is the most rapidly growing cancer in America.Although the prognosis after diagnosis is unfavorable,the chance of a successful outcome increases tremendously if detected early while the lesio...Esophageal adenocarcinoma is the most rapidly growing cancer in America.Although the prognosis after diagnosis is unfavorable,the chance of a successful outcome increases tremendously if detected early while the lesion is still dysplastic.Unfortunately,the present standard-of-care,endoscopic surveillance,has major limitations,since dysplasia is invisible,often focal,and systematic biopsies typically sample less than one percent of the esophageal lining and therefore easily miss malignancies.To solve this problem we developed a multispectral light scattering endoscopic imaging system.It surveys the entire esophageal lining and accurately detects subcellular dysplastic changes.The system combines light scattering spectroscopy,which detects and identifies invisible dysplastic sites by analyzing light scattered from epithelial cells,with rapid scanning of the entire esophageal lining using a collimated broadband light beam delivered by an endoscopically compatible fiber optic probe.Here we report the results of the first comprehensive multispectral imaging study,conducted as part of routine endoscopic procedures performed on patients with suspected dysplasia.In a double-blind study that characterized the system’s ability to serve as a screening tool,55 out of 57 patients were diagnosed correctly.In addition,a smaller double-blind comparison of the multispectral data in 24 patients with subsequent pathology at locations where 411 biopsies were collected yielded an accuracy of 90%in detecting individual locations of dysplasia,demonstrating the capability of this method to serve as a guide for biopsy.展开更多
Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentrati...Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz method.Although the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of opisthorchiasis.Methods A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV.The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted withO.viverrini were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical analyses.Results Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal FECT.Urinary OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,respectively.Cross-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence ofO.viverrini between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen ELISA.The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT(86.6%)and urinary antigen ELISA(80.5%)were similar(P>0.05).Conclusions The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis.The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening,control and elimination of opisthorchiasis,thereby contributing to a reduction in the disease burden in Southeast Asia.展开更多
基金Supported by Biotropics Malaysia Berhad,Malaysia,NN-2021-016.
文摘BACKGROUND Herbal supplements are increasingly used to manage menopausal symptoms.Physta®is a commercial herbal ingredient containing Eurycoma longifolia standardized water extract,traditionally used for vitality.Its adaptogenic and anti-inflammatory properties promote hormonal balance,physical function,and sexual health,supporting its potential benefits for menopausal health.AIM To investigate Physta®’s role in improving menopausal quality of life,mood states,and overall safety profile compared with placebo.METHODS In this 12-week,randomized,double-blind,placebo-controlled trial,138 females aged 40-55 with menopausal symptoms were randomly assigned to receive Physta®50 mg,Physta®100 mg,or placebo.MENQOL and POMS were assessed at baseline,week 6,and week 12.Safety outcomes were evaluated through biochemical tests,vital signs,and female reproductive hormonal profile.RESULTS Physta®100 mg significantly reduced total MENQOL scores by 33.9%from baseline to week 12(P=0.049)with notable improvements in the physical(-36.4%,P=0.046)and sexual(-36.3%,P=0.043)domains.Total mood disturbance also declined more in the Physta®100 mg group(-38.6%)compared with placebo(-30.1%),although not statistically significant.No significant changes were observed in the vital signs and biochemical parameters,indicating the safety and tolerability of Physta®.No significant alterations were found in the female reproductive hormone profile,supporting its hormonal neutrality.CONCLUSION Physta®100 mg improved menopausal quality of life and mood without adverse effects,supporting its potential as a safe herbal therapy.Further studies with higher doses and longer durations are needed.
基金Supported by The National Council on Science and Technology (CONACYT:85675 and 79628)Institute of Public Health(POA: 2008-2010)Research Office of Veracruzana University and Public Education Secretariat(SEP-PROMEP-UV:PTC-319)
文摘AIM:To assess expression of matrix metalloproteinases 2(MMP2)and MMP9 in gastric cancer,superficial gastritis and normal mucosa,and to measure metalloproteinase activity.METHODS:MMP2 and MMP9 mRNA expression was determined by quantitative real-time polymerase chain reaction.Normalization was carried out using three different factors.Proteins were analyzed by quantitative gelatin zymography(qGZ).RESULTS:18S ribosomal RNA(18SRNA)was very highly expressed,while hypoxanthine ribosyltransferase-1(HPRT-1)was moderately expressed.MMP2 was highly expressed,while MMP9 was not detected or lowly expressed in normal tissues,moderately or highly expressed in gastritis and highly expressed in cancer.Relative expression of 18SRNA and HPRT-1 showed no significant differences.Significant differences in MMP2 and MMP9 were found between cancer and normal tissue,but not between gastritis and normal tissue.Absolute quantification of MMP9 echoed this pattern,but differential expression of MMP2 proved conflictive.Analysis by qGZ indicated significant differences between cancer and normal tissue in MMP-2,total MMP-9,250 and 110 kDa bands.CONCLUSION:MMP9 expression is enhanced in gastric cancer compared to normal mucosa;interpretation of differential expression of MMP2 is difficult to establish.
基金partly supported by a graduate fellowship from China Scholarship Council(Grant No.201708340071)partly supported by a Career Catalyst Research Grant(Grant No.18548293)from the Susan G.Komen Foundation+1 种基金a Cancer Research Grant from the Mary Kay Foundationa Research Grant from the Elsa U.Pardee Foundation。
文摘Neutrophils,the most abundant leukocytes in human blood,are essential fighter immune cells against microbial infection.Based on the finding that neutrophils can either restrict or promote cancer progression,tumor-associated neutrophils(TAN)are classified into anti-tumor N1 and pro-tumor N2 subsets.One of the major mechanisms underlying the tumor-promoting function of N2-TANs is suppression of adaptive immune cells,in particular,cytotoxic T lymphocytes.Currently,no established methodologies are available that can unequivocally distinguish immunosuppressive TANs and granulocytic/polymorphonuclear myeloid-derived suppressor cells(G/PMN-MDSC).In view of the critical role of PMN-MDSCs in immune evasion and resistance to cancer immunotherapy,as established from data obtained with diverse cancer models,therapeutic strategies targeting these cells have been actively developed to enhance the efficacy of immunotherapy.Here,we have reviewed the available literature on strategies targeting PMN-MDSCs and summarized the findings into four categories:(1)depletion of existing PMN-MDSCs,(2)blockade of the development of PMNMDSCs,(3)blockade of PMN-MDSC recruitment,(4)inhibition of immunosuppressive function.Owing to their high mobility to inflamed organs and ability to trespass the blood-brain barrier,neutrophils are outstanding candidate carriers in nanoparticle-based therapies.Another attractive application of neutrophils in cancer therapy is the use of neutrophil membrane-derived nanovesicles as a surrogate of extracellular vesicles for more efficient and scalable drug delivery.In the second part of the review,we have highlighted recent advances in the field of neutrophil-based cancer drug delivery.Overall,we believe that neutrophil-based therapeutics are a rapidly growing area of cancer therapy with significant potential benefits.
文摘The complex and variable nature of traumatic spinal cord inju- ry （SCI） presents a unique challenge for translational research. SCI is not bound by any demographic nor is it limited to specific injury biomechanics.
基金This work was supported by the National Institutes of Health grant R01CA248033(to Xin L)Department of Defense CDMRP PCRP grants W81XWH2010312(to Xin L)+3 种基金W81XWH2010332(to Xin L)an Investigator-Initiated Research Grant from American Institute for Cancer Research(to Xin L),Indiana CTSI pilot grants(to Xin L)through the NIH NCATS CTSA grant ULITR002529an Exceptional Project Award Grant from Breast Cancer Alliance(to Xin L)CCV and IITP grants from Walther Cancer Foundation(to YZ and LD).
文摘Although immunotherapy has revolutionized cancer treatment and achieved remarkable success across many different cancer types,only a subset of patients shows meaningful clinical responses.In particular,advanced prostate cancer exhibits overwhelming de novo resistance to immune checkpoint blockade therapy.This is primarily due to the immunosuppressive tumor microenvironment of prostate cancer.Therefore,it is paramount to understand how prostate cancer cell-intrinsic mechanisms promote immune evasion and foster an immunosuppressive microenvironment.Here,we review recent findings that reveal the roles of the genetic alterations,androgen receptor signaling,cancer cell plasticity,and oncogenic pathways in shaping the immunosuppressive microenvironment and thereby driving immunotherapy resistance.Based on preclinical and clinical observations,a variety of therapeutic strategies are being developed that may illuminate new paths to enhance immunotherapy efficacy in prostate cancer.
基金supported by awards K01-AG056673,R56-AG066782-01 and R01-AG075092-01(to HF)from the National Institute on Aging of the National Institutes of Healthsupported by the award of the W81XWH1910309(to HF)from the Department of Defense.
文摘Selective vulnerability of excitatory neurons in Alzheimer’s disease(AD):AD is the most common form of dementia;however,the pathogenesis of AD is largely unknown.One of the characteristic features of AD is the formation of intracellular neurofibrillary tangles(NFTs).NFTs are abnormal accumulates of misfolded tau protein,which may eventually cause neuronal death and neurodegeneration(Jack et al.,2018).In the early stages of AD progression,not all neurons are equally vulnerable to tau aggregates.Previous studies have shown that large pyramidal neurons in the entorhinal cortex(EC)are specifically vulnerable to pathological tau accumulation(Fu et al.,2017).This selective vulnerability of excitatory neurons to tau pathology is one of the fundamental questions needed to be answered in AD research.
文摘This study was conducted to observe the genotoxic effects of aqueous, methanol, hexane and dichloromethane extracts of “belacan” (shrimp paste) taken from three local districts in Melaka, Malaysia (Kelemak, Batang Tiga & Pantai Puteri). The umu test which was used as the screening test was conducted with and without the presence of metabolic activation system. Without the presence of metabolic activation system, aqueous extracts from Kelemak showed mutagenicity activity at 5 mg/ml with IR (Induction Rate) = 1.52 ± 0.57 and the methanol extracts showed mutagenic activities at 0.625 mg/ml and 5 mg/ml, which the IR was the highest at 5 mg/ml (2.08 ± 0.09). On the other hand, samples from Batang Tiga, Melaka showed mutagenic effects at all five concentrations for the dichloromethane extract, with IR = 2.09 ± 0.64 as the highest value at 1.25 mg/ml. Methanol extracts also showed positive results at 1.25 mg/ml and 2.5 mg/ml with IR = 1.70 ± 0.33 and IR = 2.12 ± 0.51 respectively, and aqueous extract at 0.625 mg/ml with IR = 1.54 ± 0.48 and 5 mg/ml with IR = 1.74 ± 0.50. There was a significant difference of the mean values of IR between the four different types of “belacan” extracts from Batang Tiga (p < 0.05). All four “belacan” extracts from Pantai Puteri, Melaka did not show any mutagenic effect. With the presence of metabolic activation system, there was no mutagenic effect observed in all four extracts from the three districts. Further study to analyze the contents in the food samples should be done in the future to determine the possible contents in the food samples that might be responsible for the mutagenic activities.
基金supported by the Indiana CTSI Core Pilot Funding(FY24CTSIE)the Startup Funding of JL from the University of Notre Dame(START097S).
文摘The androgen receptor(AR)plays a critical role in the development and progression of prostate cancer by regulating key cellular pro-cesses such as cell proliferation and apoptosis.Although traditional AR-targeted therapies have shown initial success,acquired resis-tance remains a significant clinical challenge,often driven by AR alterations and somatic gene mutations associated with homologous recombination deficiency(HRD).Approximately 20%of advanced prostate cancer cases exhibit HRD,resulting in substantial genomic instability and complicating treatment.Fortunately,Food and Drug Administration–approved poly(ADP-ribose)polymerase inhibitors,in-cluding olaparib and rucaparib,exploit synthetic lethality to target prostate cancer with HRD,and additional drugs targeting DNA dam-age response(DDR)proteins are under development.Emerging evidence suggests that AR activity enhances DDR gene expression,with multiple DDR proteins localized near androgen-regulated regions,highlighting a close interaction between AR and DDR pathways.Consequently,recent preclinical and clinical studies have investigated combining AR-targeted therapies with treatments that induce DNA damage,such as radiation therapy,or inhibit DNA repair mechanisms.This review discusses AR's role in cellular processes,the interplay between AR and DDR,and recent advances in prostate cancer treatment strategies.
基金supported by the National Research Foundation of Korea(NRF)grant funded by the Republic of Korea government(MSIT)(No.RS-2021-NR058546 and RS-2023-00219517 to Don-Kyu Kim,No.2020R1A2C2005620,2020R1A5A2031185,and 2020M3A9G3080282 to In-Kyu Park).
文摘The liver is pivotal in protein synthesis,glucose and lipid metabolism,and detoxification.However,the liver is susceptible to both acute and chronic disorders,with chronic conditions being fatal.Chronic liver diseases(CLDs),such as liver fibrosis,which usually represents the early manifestation of cirrhosis,primarily result from hepatitis B and C viruses infections,metabolic disorders,alcohol abuse,immunemediated attacks,and cholestatic injury.The progression of liver fibrosis contributes to the development of cirrhosis,which can further lead to hepatocellular carcinoma,portal hypertension,hepatic decompensation,and hepatic encephalopathy.The extracellular matrix deposition over time leading the hepatocyte necrosis(cirrhosis)is the main structural feature of CLDs and may cause hepatic failure.Certain conditions,such as hepatitis and autoimmune diseases,may promote the rapid deterioration of liver function.Acute and chronic liver failure causes may vary,with early referral for liver transplantation improving the chance of recovery.The healthcare system need improvements to manage patients with non-alcoholic fatty liver disease and alcoholic fatty liver disease,as they have the potential to progress to cirrhosis.Both conditions involve the release of reactive oxygen species and damage-associated molecular patterns from cytokines,hepatic stellate cells,and hepatocyte autophagy,leading to prolonged inflammation.While various medications target fibrosis and liver damage,nanoparticle-based drug delivery systems offer additional promise by promoting faster liver regeneration.This review provides a comprehensive overview of the potential of nanoparticle systems as a future therapeutic approach for treating liver disorders.
基金funded by National Research Foundation of Korea(2020R1A5A2031185,2020M3A9G3080281,2022R1A2C2009385,2020M3A9G3080330,and 2022R1A6A3A01086438).
文摘Basal signal transducer and activator of transcription 3(STAT3)activation is well-documented in the tumor microenvironment(TME)due to its association with cancer prognosis[1].However,its presence and clinical relevance in the bloodstream remain unexplored.Given that STAT3-inducing cytokines,such as interleukin-6(IL-6),are often elevated in the bloodstream of various cancer patients[2,3],we aimed to investigate basal STAT3 activation in blood by developing a methodology to assess ex vivo phosphorylation of STAT3(pSTAT3ex vivo)in circulating immune cells.
基金Bio&Medical Technology Development Program of the National Research Foundation,Grant/Award Numbers:NRF-2020M3A9G3080281,NRF-2020R1A5A2031185Korean Government。
文摘Background:Increased Galectin 3-binding protein(LGALS3BP)serum levels have been used to assess hepatic fibrosis stages and the severity of hepatocellular carcinoma(HCC).Considering the crucial role of transforming growth factor-β1(TGF-β1)in the emergence of these diseases,the present study tested the hypothesis that LGALS3BP regulates the TGF-β1 signaling pathway.Methods:The expression levels of LGALS3BP and TGFB1 were analyzed in patients with metabolic dysfunction-associated steatohepatitis(MASH)and HCC.Multiple omics techniques,such as RNA-sequencing,transposaseaccessible chromatin-sequencing assay,and liquid chromatography-tandem mass spectrometry proteomics,were used to identify the regulatory mechanisms for the LGALS3BP-TGF-β1 axis.The effects of altered TGF-β1 signaling by LGALS3BP were investigated in conditional LGALS3BP-knockin and LGALS3BP-knockout mice.Results:In patients with MASH and HCC,the levels of LGALS3BP and TGFB1 exhibited positive correlations.Stimulation of LGALS3BP by the inflammatory cytokine interferonαin HCC cells or ectopic overexpression of LGALS3BP in hepatocytes promoted the expression levels of TGFB1.Aggravated fibrosis was observed in the livers of hepatocyte-specific LGALS3BP-knockin mice,with increased TGFB1 levels.LGALS3BP directly bound to and assembled integrinαV,an integral mediator required for releasing active TGF-β1 from extracellular latent complex with the rearranged F-actin cytoskeleton.The released TGF-β1 activated JunB transcription factor,which in turn promoted the TGF-β1 positive feedback loop.LGALS3BP deletion in the hepatocytes downregulated TGF-β1 signaling and CCl4 induced fibrosis.Moreover,LGALS3BP depletion hindered hepatocarcinogenesis by limiting the availability of fibrogenic TGF-β1.Conclusion:LGALS3BP plays a crucial role in hepatic fibrosis and carcinogenesis by controlling the TGF-β1 signaling pathway,making it a promising therapeutic target in TGF-β1-related diseases.
基金funding sources:R00-CA230202(M.K.S.L.)IMPACT Award(O'Neal Comprehensive Cancer Center,M.K.S.L.)the Fine Family Philanthropic Grant(M.K.S.L),UAB Blazer Fellowship(M.K.)and T32-EB023872(M.K.).
文摘The ovarian tumor microenvironment plays a critical yet is poorly understood role in the regulation of cancer cell behaviors including proliferation,migration,and response to chemotherapy treatments.Ovarian cancer is the deadliest gynecological cancer,due to diagnosis at late stages of the disease and increased resistance to chemotherapies for recurrent disease.Understanding how the tumor microenvironment(TME)interacts with biomechanical forces to drive changes to ovarian cancer cell behaviors could elucidate novel treatment strategies for this patient population.Additionally,limitations in current preclinical models of the ovarian TME do not permit investigation of crosstalk between signaling pathways and mechanical forces.Our study focused on uncovering how strains and hyaluronic acid(HA)interact to signal through the CD44 receptor to alter ovarian cancer cell growth,migration,and response to a commonly used chemotherapy,paclitaxel.Using an advanced 3D in vitro model,we were able to identify how interactions of strain and HA as in the TME synergistically drive enhanced proliferation and migration in an ovarian tumor model line,while decreasing response to paclitaxel treatment.This study demonstrates the importance of elucidating how the mechanical forces present in the ovarian TME drive disease progression and response to treatment.
基金supported by the American Lebanese Syrian Associated Charities (ALSAC),St.Jude Children0s Research Hospitalthe U.S. National Institutes of Health (Grants GM086415,GM110034,GM118041 and P30-CA21765)
文摘The pregnane X receptor(PXR) plays an important and diverse role in mediating xenobiotic induction of drug-metabolizing enzymes and transporters.Several protein isoforms of PXR exist,and they have differential transcriptional activity upon target genes; transcript variants 3(PXR3) and 4(PXR4) do not induce target gene expression,whereas transcript variants 1(PXR1) and 2(PXR2) respond to agonist by activating target gene expression.PXR protein variants also display differences in protein–protein interactions; PXR1 interacts with p53,whereas PXR3 does not.Furthermore,the transcript variants of PXR that encode these protein isoforms are differentially regulated by methylation and deletions in the respective promoters of the variants,and their expression differs in various human cancers and also in cancerous tissue compared to adjacent normal tissues.PXR1 and PXR4 m RNA are downregulated by methylation in cancerous tissue and have divergent effects on cellular proliferation when ectopically overexpressed.Additional detailed and comparative mechanistic studies are required to predict the effect of PXR transcript variant expression on carcinogenesis,therapeutic response,and the development of toxicity.
基金supported,in part,by ALSAC and by the National Institutes of Health grants R35-GM118041 and P30-CA21765.
文摘Cytochrome P450(CYP)enzymes function to catalyze a wide range of reactions,many of which are critically important for drug response.Members of the human cytochrome P4503A(CYP3A)family are particularly important in drug clearance,and they collectively metabolize more than half of all currently prescribed medications.The ability of these enzymes to bind a large and structurally diverse set of compounds increases the chances of their modulating or facilitating drug metabolism in unfavorable ways.Emerging evidence suggests that individual enzymes in the CYP3A family play discrete and important roles in catalysis and disease progression.Here we review the similarities and differences among CYP3A enzymes with regard to substrate recognition,metabolism,modulation by small molecules,and biological consequence,highlighting some of those with clinical significance.We also present structural perspectives to further characterize the basis of these comparisons.
文摘Engineered functional neural interfaces （fNIs） serve as essential abiotic-biotic transducers between an engineered system and the nervous system. They convert external physical stimuli to cellular signals in stimulation mode or read out biological processes in recording mode. Information can be exchanged using electricity, light, magnetic fields, mechanical forces, heat, or chemical signals. fNIs have found applications for studying processes in neural circuits from cell cultures to organs to whole organisms, fNI-facilitated signal transduction schemes, coupled with easily manipulable and observable external physical signals, have attracted considerable attention in recent years. This enticing field is rapidly evolving toward miniaturization and biomimicry to achieve long-term interface stability with great signal transduction efficiency. Not only has a new generation of neuroelectrodes been invented, but the use of advanced fNIs that explore other physical modalities of neuromodulation and recording has begun to increase. This review covers these exciting developments and applications of fNIs that rely on nanoelectrodes, nanotransducers, or bionanotransducers to establish an interface with the nervous system. These nano fNIs are promising in offering a high spatial resolution, high target specificity, and high communication bandwidth by allowing for a high density and count of signal channels with minimum material volume and area to dramatically improve the chronic integration of the fNI to the target neural tissue. Such demanding advances in nano fNIs will greatly facilitate new opportunities not only for studying basic neuroscience but also for diagnosing and treating various neurological diseases.
文摘Objective:Chronic rhinosinusitis(CRS)involves inflammation of the nasal and para-nasal mucosa.Due to its heterogeneous nature,unknown pathogenesis,and high recurrence rate,effective treatment is difficult.Nasal cytology is presently not a part of the routine diagnosis or treatment decision for CRS.Data sources:A literature search was performed for published papers in English between January 1990 and June 2019 using MEDLINE.Study sdection:Terms used were chronic rhinosinusids,eosinophils,etiology,immunopathology,inflammation,mast cells,nasal cytology,polyps,and treatment.Both reviews and original articles were collected and studied.Results:There is no standard nasal fluid,mucus sampling,or staining techniques for identifying inflammatory cell types.Results were divergent from different countries.Moreover,the main focus of these papers on the cells in nasal washings was eosinophils,with infrequent mentioning of other cell types that may imply different etiology and pathology.The heterogeneous cell profile of CRS and the role of mast cells have been unappreciated due to the lack of specific immunohistochemical technique or study of its unique mediators.Conclusions:Nasal cytology could help distinguish the type and the activation state of inflammatory cells.Thus it can help in providing a clearer picture of CRS pathogenesis,identifying different patient groups,and developing effective treatments.
基金This research was supported by R01 MH 087583 and R01 MH 099085 to MK.
文摘DNA methylation has been identified as a powerful and activity-dependent regulator of changes in the brain that may underlie neuroadaptations in response to various types of stimuli,including exposure to drugs of abuse.Indeed,the medial prefrontal cortex(mPFC)projections to the nucleus accumbens(NAc)are critically important for reinstated cocaine-seeking in a rodent model of cocaine relapse.This circuitry undergoes several epigenetic modifications following cocaine exposure,including changes in DNA methylation that are associated with drug-seeking behavior.We have previously shown that methyl supplementation via L-Methionine(MET)administration attenuates cocaine-seeking behavior and reverses expression and methylation patterns of the immediate early gene c-fos,suggesting that MET may act by altering the excitability of this circuitry during cocaine reinstatement.In the current study,male rats were microinjected with an adeno-associated virus overexpressing halorhodopsin in the mPFC,optical fibers were surgically implanted into the NAc,and the rats were given injections of MET daily.Rats underwent acquisition of cocaine self-administration(0.75 mg/kg/infusion,2-h sessions)followed by extinction training in the absence of drug-paired cues.Two reinstatement tests were conducted:cue-induced reinstatement without optogenetic manipulations and cocaine-primed reinstatement with optogenetic inhibition of mPFC-to-NAc projections.There were no group differences before the cocaine-primed reinstatement session,and all groups showed robust cue-induced reinstatement.Both rats treated with MET and rats that received mPFC-to-NAc inhibition showed an abolishment of cocaine-primed reinstatement,suggesting that systemic methyl supplementation may act through this critical circuity.
基金supported by the US National Institutes of Health grants R01 EB003472,R01 EB025173 and R01 CA205431the US National Science Foundation grants EFRI-1240410,CBET-1402926 and CBET-1605116.
文摘Esophageal adenocarcinoma is the most rapidly growing cancer in America.Although the prognosis after diagnosis is unfavorable,the chance of a successful outcome increases tremendously if detected early while the lesion is still dysplastic.Unfortunately,the present standard-of-care,endoscopic surveillance,has major limitations,since dysplasia is invisible,often focal,and systematic biopsies typically sample less than one percent of the esophageal lining and therefore easily miss malignancies.To solve this problem we developed a multispectral light scattering endoscopic imaging system.It surveys the entire esophageal lining and accurately detects subcellular dysplastic changes.The system combines light scattering spectroscopy,which detects and identifies invisible dysplastic sites by analyzing light scattered from epithelial cells,with rapid scanning of the entire esophageal lining using a collimated broadband light beam delivered by an endoscopically compatible fiber optic probe.Here we report the results of the first comprehensive multispectral imaging study,conducted as part of routine endoscopic procedures performed on patients with suspected dysplasia.In a double-blind study that characterized the system’s ability to serve as a screening tool,55 out of 57 patients were diagnosed correctly.In addition,a smaller double-blind comparison of the multispectral data in 24 patients with subsequent pathology at locations where 411 biopsies were collected yielded an accuracy of 90%in detecting individual locations of dysplasia,demonstrating the capability of this method to serve as a guide for biopsy.
基金supported by the Cholangiocarcinoma Research Institute,Khon Kaen University,Thailand.This project is funded by the National Science Research Council of Thailand(NRCT)the Post-Doctoral Training Program from Khon Kaen University,Thailand(PD2565-02-01)supported by the Thailand Centre of Excellence for Life Sciences(TCELS)SDT-R was funded by the Wellcome Trust ISSF grant at Imperial College London.
文摘Background Screening for opisthorchiasis,a parasitic worm infection affecting many millions of people in Southeast Asia,has traditionally relied on faecal egg examination such as the formalin-ethyl acetate concentration technique(FECT)and Kato-Katz method.Although the urinary enzyme-linked immunosorbent assay(ELISA)has been used more recently,we developed a urinary antigen-based rapid diagnostic test(RDT)to simplify diagnosis and as a point-of-care testing(POCT)and field applications for surveillance and control of opisthorchiasis.Methods A urinaryOpisthorchis viverrini(OV)-RDT was developed using immunochromatographic methodology with a specific monoclonal antibody against OV.The diagnostic performance of the urinary OV-RDT was compared to that of quantitative faecal FECT and urinary antigen ELISA(n=493).Cross-reactivities of urinary OV-RDT with other helminthiases coexisted withO.viverrini were determined(n=96).A field trial in the application of urinary OV-RDT was compared with urinary antigen ELISA at baseline screening and assessment of drug treatment outcomes in opisthorchiasis(n=1629).The McNemar chi-square,Kruskal-Wallis and Cohen’s kappa coefficient(κ-value)tests were used for statistical analyses.Results Urinary OV-RDT had sensitivity of 94.2%and specificity of 93.2%,compared to faecal FECT.Urinary OV-RDT had high diagnostic agreement(Kappa=0.842-0.874,P<0.001)and quantitative correlation with urinary antigen ELISA(Kruskal-Wallis tests=316.2,P<0.0001)and faecal FECT(Kruskal-Wallis tests=362.3,P<0.0001).The positive rates by OV-RDT,ELISA and FECT were 48.9%,52.5%and 49.3%,respectively.Cross-reactions of urinary OV-RDT with other helminthiases were few(2%).Field trials of urinary OV-RDT yielded comparable prevalence ofO.viverrini between urinary OV-RDT(53.2%)and urinary antigen ELISA(54.0%).OV screening showed high diagnostic agreement(kappa>0.8,P<0.0001)between urinary OV-RDT and urinary antigen ELISA.The cure rates of opisthorchiasis at 1 month post-praziquantel treatment determined by urinary OV-RDT(86.6%)and urinary antigen ELISA(80.5%)were similar(P>0.05).Conclusions The urinary OV-RDT test has high potential as a new tool for screening and evaluating treatment outcomes in opisthorchiasis.The ease of sample collection and simplicity of urinary OV-RDT may facilitate mass screening,control and elimination of opisthorchiasis,thereby contributing to a reduction in the disease burden in Southeast Asia.
