Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability.

Nucleocytoplasmic transport (NCT), the facilitated diffusion of cargo molecules between the nucleus and cytoplasm through nuclear pore complexes (NPCs), enables numerous fundamental eukaryotic cellular processes. Ran GTPase uses cellular energy in the direct form of GTP to create a gradient across the nuclear envelope (NE) that drives the majority of NCT. We report here that changes in GTP availability resulting from altered cellular physiology modulate the rate of NCT, as monitored using synthetic and natural cargo, and the dynamics of Ran itself. Cell migration, cell spreading, and/or modulation of the cytoskeleton or its connection to the nucleus alter GTP availability and thus rates of NCT, regulating RNA export and protein synthesis. These findings support a model in which changes in cellular physiology that alter GTP availability can regulate the rate of NCT, impacting fundamental cellular processes that extensively utilize NCT.

Stiffness assisted cell-matrix remodeling trigger 3D mechanotransduction regulatory programs.

Engineered matrices provide a valuable platform to understand the impact of biophysical factors on cellular behavior such as migration, proliferation, differentiation, and tissue remodeling, through mechanotransduction. While recent studies have identified some mechanisms of 3D mechanotransduction, there is still a critical knowledge gap in comprehending the interplay between 3D confinement, ECM properties, and cellular behavior. Specifically, the role of matrix stiffness in directing cellular fate in 3D microenvironment, independent of viscoelasticity, microstructure, and ligand density remains poorly understood. To address this gap, we designed a nanoparticle crosslinker to reinforce collagen-based hydrogels without altering their chemical composition, microstructure, viscoelasticity, and density of cell-adhesion ligand and utilized it to understand cellular dynamics. This crosslinking mechanism utilizes nanoparticles as crosslink epicenter, resulting in 10-fold increase in mechanical stiffness, without other changes. Human mesenchymal stem cells (hMSCs) encapsulated in 3D responded to mechanical stiffness by displaying circular morphology on soft hydrogels (5 kPa) and elongated morphology on stiff hydrogels (30 kPa). Stiff hydrogels facilitated the production and remodeling of nascent extracellular matrix (ECM) and activated mechanotransduction cascade. These changes were driven through intracellular PI3AKT signaling, regulation of epigenetic modifiers and activation of YAP/TAZ signaling. Overall, our study introduces a unique biomaterials platform to understand cell-ECM mechanotransduction in 3D for regenerative medicine as well as disease modelling.

Dynamically Cross-Linked Granular Hydrogels for 3D Printing and Therapeutic Delivery.

Granular hydrogels have recently emerged as promising biomaterials for tissue engineering and 3D-printing applications, addressing the limitations of bulk hydrogels while exhibiting desirable properties such as injectability and high porosity. However, their structural stability can be improved with post-injection interparticle cross-linking. In this study, we developed granular hydrogels with interparticle cross-linking through reversible and dynamic covalent bonds. We fragmented photo-cross-linked bulk hydrogels to produce aldehyde or hydrazide-functionalized microgels using chondroitin sulfate. Mixing these microgels facilitated interparticle cross-linking through reversible hydrazone bonds, providing shear-thinning and self-healing properties for injectability and 3D printing. The resulting granular hydrogels displayed high mechanical stability without the need for secondary cross-linking. Furthermore, the porosity and sustained release of growth factors from these hydrogels synergistically enhanced cell recruitment. Our study highlights the potential of reversible interparticle cross-linking for designing injectable and 3D printable therapeutic delivery scaffolds using granular hydrogels. Overall, our study highlights the potential of reversible interparticle cross-linking to improve the structural stability of granular hydrogels, making them an effective biomaterial for use in tissue engineering and 3D-printing applications.

Dynamically crosslinked thermoresponsive granular hydrogels.

Granular hydrogels are a promising biomaterial for a wide range of biomedical applications, including tissue regeneration, drug/cell delivery, and 3D printing. These granular hydrogels are created by assembling microgels through the jamming process. However, current methods for interconnecting the microgels often limit their use due to the reliance on postprocessing for crosslinking through photoinitiated reactions or enzymatic catalysis. To address this limitation, we incorporated a thiol-functionalized thermo-responsive polymer into oxidized hyaluronic acid microgel assemblies. The rapid exchange rate of thiol-aldehyde dynamic covalent bonds allows the microgel assembly to be shear-thinning and self-healing, with the phase transition behavior of the thermo-responsive polymer serving as secondary crosslinking to stabilize the granular hydrogels network at body temperature. This two-stage crosslinking system provides excellent injectability and shape stability, while maintaining mechanical integrity. In addition, the aldehyde groups of the microgels act as covalent binding sites for sustained drug release. These granular hydrogels can be used as scaffolds for cell delivery and encapsulation, and can be 3D printed without the need for post-printing processing to maintain mechanical stability. Overall, our work introduces thermo-responsive granular hydrogels with promising potential for various biomedical applications.

Intraoperative application of optical coherence tomography for lung tumor.

On-site instant determination of benign or malignant tumors for deciding the types of resection is crucial during pulmonary surgery. We designed a portable spectral-domain optical coherence tomography (SD-OCT) system to do real-time scanning intraoperatively for the distinction of fresh tumor specimens in the lung. A total of 12 ex vivo lung specimens from six patients were enrolled. Three patients were diagnosed with invasive adenocarcinoma (IA), while the others were benign. After OCT-imaged reconstruction, we compared the qualitative morphology of OCT and histology among malignant, benign, and normal tissues. In addition, through analysis of the quantitative data, a discrete difference in optical attenuation coefficients around the junctional surface was shown by our data processing. This study demonstrated a feasible OCT-assisted resection guide by a rapid on-site tumor diagnosis. The results indicate that future deep learning of OCT-captured image systems able to improve diagnostic and therapeutic efficiency is warranted.

Transitions in Frailty and 4-Year Mortality Risk in Taiwan Longitudinal Study on Aging.

OBJECTIVES: To explore the associations of (1) the frailty phenotype or frailty index transition with cause-specific mortality, and (2) different combinations of transition in frailty phenotype and frailty index with all-cause mortality. DESIGN: Retrospective cohort study. SETTING AND PARTICIPANTS: Data from 3529 respondents aged >50 years who completed the 1999 and 2003 surveys of the Taiwan Longitudinal Study on Aging were analyzed. METHODS: Cox regression and subdistribution hazard models were constructed to investigate frailty phenotype or frailty index transitions (by categories of frailty phenotype, absolute and percentage changes in frailty index, and combined categories of the 2 measurements) and subsequent 4-year all-cause and cause-specific mortality, respectively. RESULTS: Among the frailty phenotype transition groups, the improved frailty group had overall mortality risk comparable to that of the maintained robustness/prefrailty group [hazard ratio (HR): 0.9; 95% CI: 0.7-1.2] and lower risk of mortality due to organ failure (HR: 0.4; 95% CI: 0.2-0.8; P = .015), whereas the worsened frailty group had the highest risk of all-cause mortality and death from infection, malignancy, cardiometabolic/cerebrovascular diseases, and other causes (HR: 1.8-3.7; all P < .03). The rapidly increased frailty index group had significantly higher all-cause and every cause-specific mortality than the decreased frailty index group (HR: 1.8-7.7; all P < .05). When frailty phenotype and frailty index transition groups were combined, participants with worsened frailty/rapidly increased frailty index had increased risk under the same frailty index/frailty phenotype transition condition, particularly for large changes in each factor (HR: 1.5-2.2; P < .01 for worsened frailty; 1.7-4.5, P < .03 for rapidly increased frailty index). CONCLUSIONS AND IMPLICATIONS: We found that considering both frailty phenotype and frailty index provided best mortality prediction. These associations were independent of baseline frailty status and comorbidities. Nevertheless, even capturing transitions in frailty phenotype or frailty index only can provide good mortality prediction, which supported adopting these approaches in different clinical settings.

Nucleocytoplasmic transport rates are regulated by cellular processes that modulate GTP availability.

Nucleocytoplasmic transport (NCT), the facilitated diffusion of cargo molecules between the nucleus and cytoplasm through nuclear pore complexes (NPCs), enables numerous fundamental eukaryotic cellular processes. Ran GTPase uses cellular energy in the direct form of GTP to create a gradient across the nuclear envelope (NE) that drives the majority of NCT. We report here that changes in GTP availability resulting from altered cellular physiology modulate the rate of NCT, as monitored using synthetic and natural cargo, and the dynamics of Ran itself. Cell migration, cell spreading and/or modulation of the cytoskeleton or its connection to the nucleus alter GTP availability and thus rates of NCT, regulating RNA export and protein synthesis. These findings support a model in which changes in cellular physiology that alter GTP availability can regulate the rate of NCT, impacting fundamental cellular processes that extensively utilize NCT.

Nasopharyngeal Large Cell Neuroendocrine Carcinoma Synchronized With Nasopharyngeal Squamous Cell Carcinoma: A Case Report and Review of Literature.

Neuroendocrine carcinomas (NECs) are poorly differentiated neuroendocrine tumors of the upper respiratory tract. We present an extremely rare case of nasopharyngeal large cell neuroendocrine carcinoma (LCNEC) synchronized with nasopharyngeal squamous cell carcinoma (SCC). Both SCC and LCNEC are associated with Epstein-Barr virus (EBV) infection, supported by the positive result of Epstein-Barr encoding region in-situ hybridization. Strong correlation is found between EBV infection and nasopharyngeal malignancies. Furthermore, the EBV status might be a crucial prognostic factor in nasopharyngeal LCNEC. EBV-positive LCNEC is effective to chemoradiotherapy, and may have preferable outcome than EBV-negative LCNEC arising in the nasopharynx or other sites. The recognition of the EBV status is important for patients to receive appropriate treatment.

All-Printed Ultrahigh-Responsivity MoS2 Nanosheet Photodetectors Enabled by Megasonic Exfoliation.

Printed 2D materials, derived from solution-processed inks, offer scalable and cost-effective routes to mechanically flexible optoelectronics. With micrometer-scale control and broad processing latitude, aerosol-jet printing (AJP) is of particular interest for all-printed circuits and systems. Here, AJP is utilized to achieve ultrahigh-responsivity photodetectors consisting of well-aligned, percolating networks of semiconducting MoS2 nanosheets and graphene electrodes on flexible polyimide substrates. Ultrathin (≈1.2 nm thick) and high-aspect-ratio (≈1 µm lateral size) MoS2 nanosheets are obtained by electrochemical intercalation followed by megasonic atomization during AJP, which not only aerosolizes the inks but also further exfoliates the nanosheets. The incorporation of the high-boiling-point solvent terpineol into the MoS2 ink is critical for achieving a highly aligned and flat thin-film morphology following AJP as confirmed by grazing-incidence wide-angle X-ray scattering and atomic force microscopy. Following AJP, curing is achieved with photonic annealing, which yields quasi-ohmic contacts and photoactive channels with responsivities exceeding 103  A W-1 that outperform previously reported all-printed visible-light photodetectors by over three orders of magnitude. Megasonic exfoliation coupled with properly designed AJP ink formulations enables the superlative optoelectronic properties of ultrathin MoS2 nanosheets to be preserved and exploited for the scalable additive manufacturing of mechanically flexible optoelectronics.

Repurposing Multiple-Molecule Drugs for COVID-19-Associated Acute Respiratory Distress Syndrome and Non-Viral Acute Respiratory Distress Syndrome via a Systems Biology Approach and a DNN-DTI Model Based on Five Drug Design Specifications.

The coronavirus disease 2019 (COVID-19) epidemic is currently raging around the world at a rapid speed. Among COVID-19 patients, SARS-CoV-2-associated acute respiratory distress syndrome (ARDS) is the main contribution to the high ratio of morbidity and mortality. However, clinical manifestations between SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS are quite common, and their therapeutic treatments are limited because the intricated pathophysiology having been not fully understood. In this study, to investigate the pathogenic mechanism of SARS-CoV-2-associated ARDS and non-SARS-CoV-2-associated ARDS, first, we constructed a candidate host-pathogen interspecies genome-wide genetic and epigenetic network (HPI-GWGEN) via database mining. With the help of host-pathogen RNA sequencing (RNA-Seq) data, real HPI-GWGEN of COVID-19-associated ARDS and non-viral ARDS were obtained by system modeling, system identification, and Akaike information criterion (AIC) model order selection method to delete the false positives in candidate HPI-GWGEN. For the convenience of mitigation, the principal network projection (PNP) approach is utilized to extract core HPI-GWGEN, and then the corresponding core signaling pathways of COVID-19-associated ARDS and non-viral ARDS are annotated via their core HPI-GWGEN by KEGG pathways. In order to design multiple-molecule drugs of COVID-19-associated ARDS and non-viral ARDS, we identified essential biomarkers as drug targets of pathogenesis by comparing the core signal pathways between COVID-19-associated ARDS and non-viral ARDS. The deep neural network of the drug-target interaction (DNN-DTI) model could be trained by drug-target interaction databases in advance to predict candidate drugs for the identified biomarkers. We further narrowed down these predicted drug candidates to repurpose potential multiple-molecule drugs by the filters of drug design specifications, including regulation ability, sensitivity, excretion, toxicity, and drug-likeness. Taken together, we not only enlighten the etiologic mechanisms under COVID-19-associated ARDS and non-viral ARDS but also provide novel therapeutic options for COVID-19-associated ARDS and non-viral ARDS.

Validation of snoring detection using a smartphone app.

PURPOSE: Snoring is closely related to obstructive sleep apnea in adults. The increasing abundance and availability of smartphone technology has facilitated the examination and monitoring of snoring at home through snoring apps. However, the accuracy of snoring detection by snoring apps is unclear. This study explored the snoring detection accuracy of Snore Clock-a paid snoring detection app for smartphones. METHODS: Snoring rates were detected by smartphones that had been installed with the paid app Snore Clock. The app provides information on the following variables: sleep duration, snoring duration, snoring loudness (in dB), maximum snoring loudness (in dB), and snoring duration rate (%). In brief, we first reviewed the snoring rates detected by Snore Clock; thereafter, an ear, nose, and throat specialist reviewed the actual snoring rates by using the playback of the app recordings. RESULTS: In total, the 201 snoring records of 11 patients were analyzed. Snoring rates measured by Snore Clock and those measured manually were closely correlated (r = 0.907). The mean snoring detection accuracy rate of Snore Clock was 95%, with a positive predictive value, negative predictive value, sensitivity, and specificity of 65% ± 35%, 97% ± 4%, 78% ± 25%, and 97% ± 4%, respectively. However, the higher the snoring rates, the higher were the false-negative rates for the app. CONCLUSION: Snore Clock is compatible with various brands of smartphones and has a high predictive value for snoring. Based on the strong correlation between Snore Clock and manual approaches for snoring detection, these findings have validated that Snore Clock has the capacity for at-home snoring detection.

Conjugation of Polysulfobetaine via Poly(pyrogallol) Coatings for Improving the Antifouling Efficacy of Biomaterials.

Antifouling treatment is critical to certain biomedical devices for their functions and patients' life. Facial, versatile, and universal coating methods to conjugate antifouling materials on a wide variety of biomaterials are beneficial for the fabrication of low-fouling biomedical devices. We developed a simple one-step coating method for surface conjugation of zwitterionic poly(sulfobetaine) via deposition of self-polymerized pyrogallol (PG). Poly(pyrogallol) could deposit copolymers of sulfobetaine methacrylate and aminoethyl methacrylate (pSBAE) on various biomaterials. pSBAE coatings inhibited as high as 99.8% of the adhesion of L929 cells and reduced protein adsorption significantly. The resistance against L929 cell adhesion was increased with increasing coating time and was positively correlated with the surface hydrophilicity and film thickness. Such a coating was robust to resist harsh sterilization conditions and stable for long-term storage in phosphate-buffered saline. We expect that the simple low-fouling pSBAE coating is applicable to the manufacture of medical devices.

Effects of incorporating multidomain interventions into integrated primary care on quality of life: a randomised controlled trial.

BACKGROUND: Integrating primary prevention into care pathways for older adults is a core strategy of healthy ageing, but evidence remains limited. We aimed to determine whether incorporating a multidomain intervention into primary health care could improve standard value-based health outcomes and quality of life. METHODS: For this Taiwan Integrated Geriatric Care (TIGER) study, a pragmatic randomised controlled trial, we recruited community-dwelling outpatients aged 65 years or older with at least three chronic medical conditions. We excluded people with malignancies undergoing chemotherapy, people with a life expectancy of less than 12 months, or people who were insufficiently able to communicate with study staff. Participants were randomly assigned (1:1) to usual care or to the integrated multidomain intervention using block randomisation. The integrated multidomain intervention entailed 16 2-h sessions per year, comprising communal physical exercise, cognitive training, nutrition and disease education, plus individualised treatment by specialists in integrated geriatric care. The primary outcome was changes from baseline quality of life, based on 36-item Short Form Health Survey (SF-36) scores, at 3, 6, 9, and 12 months. Intervention effects were analysed per protocol using a generalised linear mixed model. This trial is registered with ClinicalTrials.gov, NCT03528005. FINDINGS: Between June 25, 2018, and Feb 15, 2019, 628 participants were screened, of whom 398 were assigned to the integrated multidomain intervention (n=199) or to usual care (n=199). 335 (84%) participants completed the 12-month follow-up. Compared with the usual care group, the integrated multidomain intervention group had significantly higher mean SF-36 physical component scores across all timepoints (overall difference 0·8, 95% CI 0·2-1·5; p=0·010), but differences at 3, 6, 9, and 12 months did not reach statistical significance. The SF-36 mental component scores did not differ significantly overall, but were significantly higher in the integrated multidomain intervention group at the 12-month follow-up (55·3 [SD 7·6] vs 57·2 [7·0]; p=0·019). No serious adverse events occurred. INTERPRETATION: Incorporating multidomain interventions into integrated health care improved quality of life. Our standardised protocol is amenable to inclusion in policies to promote value-based care and healthy ageing. FUNDING: National Health Research Institutes, Taiwan, and Ministry of Science and Technology, Taiwan.

Curcumin-induced antitumor effects on triple-negative breast cancer patient-derived xenograft tumor mice through inhibiting salt-induced kinase-3 protein.

This study demonstrated for the first time that curcumin effectively inhibits the growth of triple-negative breast cancer (TNBC) tumors by inhibiting the expression of salt-induced kinase-3 (SIK3) protein in patient-derived xenografted tumor mice (TNBC-PDX). For TNBC patients, chemotherapy is the only option for postoperative adjuvant treatment. In this study, we detected the SIK3 mRNA expression in paired-breast cancer tissues by qPCR analysis. The results revealed that SIK3 mRNA expression was significantly higher in tumor tissues when compared to the normal adjacent tissues (73.25 times, n = 183). Thus, it is proposed for the first time that the antitumor effect induced by curcumin by targeting SIK3 can be used as a novel strategy for the therapy of TNBC tumors. In vitro mechanism studies have shown that curcumin (>25 µM) inhibits the SIK3-mediated cyclin D upregulation, thereby inhibiting the G1/S cell cycle and arresting TNBC (MDA-MB-231) cancer cell growth. The SIK3 overexpression was associated with increased mesenchymal markers (i.e., Vimentin, α-SMA, MMP3, and Twist) during epithelial-mesenchymal transition (EMT). Our results demonstrated that curcumin inhibits the SIK3-mediated EMT, effectively attenuating the tumor migration. For clinical indications, dietary nutrients (such as curcumin) as an adjuvant to chemotherapy should be helpful to TNBC patients because the current trend is to shrink the tumor with preoperative chemotherapy and then perform surgery. In addition, from the perspective of chemoprevention, curcumin has excellent clinical application value.

Insulinoma-associated Protein 1 Expression and Its Diagnostic Significance in Female Genital Tract Neuroendocrine Carcinomas.

Neuroendocrine carcinomas (NECs) are rare, but aggressive malignant tumors of the female genital tract, especially in the uterine the cervix. Beside histologic morphology, positivity of neuroendocrine markers with immunohistochemistry plays an important role in diagnosis of NECs. Insulinoma-associated protein 1 (INSM1) is a novel marker reported to be widely expressed in a variety of neuroendocrine tumors. A previous study also suggested INSM1 has superior performance to conventional neuroendocrine markers in cervical NECs. In our present study, comparison between immunomarkers was performed in female genital tract NECs. Forty-nine patients with gynecologic NECs (4 vagina, 39 cervix, 5 endometrium, 1 ovary) were included from 1993 to 2019 at our center. Immunohistochemistry was performed with INSM1, CD56, synaptophysin (SYN), chromogranin-A (CgA), and thyroid transcription factor 1 (TTF1). The results show INSM1 has superior sensitivity and intensity compared with CD56, SYN, CgA, and TTF1 in cervical small cell NECs, but not in large cell NECs. In contrast to cervical NECs, INSM1 immunohistochemistry shows only focal and weak staining in endometrial NECs. Our result suggested INSM1 is a sensitive marker which can be used as first-line test in histologic suspicious cervical cases, especially small cell NECs. However, negative INSM1 stain does not exclude the possibility of NECs. In endometrial NECs, conventional panel with CD56, SYN, CgA has better diagnostic performance than INSM1 alone.

Innovative Head-Mounted System Based on Inertial Sensors and Magnetometer for Detecting Falling Movements.

This work presents a fall detection system that is worn on the head, where the acceleration and posture are stable such that everyday movement can be identified without disturbing the wearer. Falling movements are recognized by comparing the acceleration and orientation of a wearer's head using prespecified thresholds. The proposed system consists of a triaxial accelerometer, gyroscope, and magnetometer; as such, a Madgwick's filter is adopted to improve the accuracy of the estimation of orientation. Moreover, with its integrated Wi-Fi module, the proposed system can notify an emergency contact in a timely manner to provide help for the falling person. Based on experimental results concerning falling movements and activities of daily living, the proposed system achieved a sensitivity of 96.67% in fall detection, with a specificity of 98.27%, and, therefore, is suitable for detecting falling movements in daily life.

First insights on value-based healthcare of elders using ICHOM older person standard set reporting.

BACKGROUND: Clinical guidelines for specific conditions fragment care provision for elders. The International Consortium for Health Outcomes Measurement (ICHOM) has developed a global standard set of outcome measures for comprehensive assessment of older persons. The goal of this study was to report value-based health metrics in Taiwan using this ICHOM toolset. METHODS: The cross-sectional study of baseline data excerpted from a prospective longitudinal cohort, which recruited people ≥65 years old with ≥3 chronic medical conditions between July and December 2018. All participants received measurements of physical performance, anthropometric characteristics, health-related behaviors, Charlson Comorbidity Index, and Montreal Cognitive Assessment. The ICHOM toolset comprises three tiers: 1 includes frailty and having chosen a preferred place of death; 2 includes polypharmacy, falls, and participation in decision-making; and 3 includes loneliness, activities of daily living, pain, depression, and walking speed. These items were converted into a 0-10 point value-based healthcare score, with high value-based health status defined as ≥8/10 points. RESULTS: Frequencies of individual ICHOM indicators were: frail 11.7%, chose preferred place of death 14.4%, polypharmacy 31.5%, fell 17.1%, participated in decision-making 81.6%, loneliness 26.8%, limited activities of daily living 22.4%, pain 10.4%, depressed mood 13.0%, and slowness 38.5%. People with high disease burden (OR 0.40, 95% CI 0.21-0.76, p = 0.005) or cognitive impairment (OR 0.49, 95%CI 0.27-0.87, p = 0.014) were less likely to have high value-based healthcare status. CONCLUSIONS: The ICHOM Standard Set Older Person health outcome measures provide an opportunity to shift from a disease-centric medical paradigm to whole person-focused goals. This study identified advanced age, chronic disease burden and cognitive impairment as important barriers to achieving high value-based healthcare status.

Concurrent bilateral testicular hamartomas and serous borderline tumors in a patient with complete androgen insensitivity syndrome: a case report and review of the literature.

We report a case of complete androgen insensitivity syndrome (CAIS) accompanied by serous borderline tumors in a 75-year-old patient. Müllerian epithelial tumors are extremely rare condition in CAIS patients with only a few case reports. We report a case of late-diagnosed testicular feminization with hamartomas, and the first report of serous tumor with borderline malignant potential in such cases.

The use of dehydroepiandrosterone-treated rats is not a good animal model for the study of metabolic abnormalities in polycystic ovary syndrome.

OBJECTIVE: Hyperandrogenism is the hallmark of polycystic ovary syndrome (PCOS). The use of dehydroepiandrosterone (DHEA)-treated rats is thought to be a suitable animal model to study PCOS. In the present study, we assessed the severity of reproductive and metabolic abnormalities in DHEA-treated rats. MATERIAL AND METHODS: Immature female Sprague-Dawley rats were divided into control and DHEA-treated groups. Reproductive parameters including estrus cycle and sex hormones were measured after sexual maturity. Adiposity, insulin sensitivity, and plasma lipid profiles were analyzed to assess metabolic profiles. After sacrifice, the insulin signaling pathway and lipogenic genes were analyzed by immunoblotting and polymerase chain reaction, respectively. RESULTS: An abnormal estrus cycle was observed in the DHEA-treated rats. DHEA treatment also increased plasma testosterone levels and caused multiple cystic follicle formation, which is compatible with the definition of PCOS. There were no significant changes in fasting glucose, fasting insulin, plasma lipid profiles, and blood pressure levels. The adiposity of the DHEA-treated rats was also lower than in the control rats. Moreover, glucose tolerance and insulin sensitivity were only mildly impaired in the DHEA-treated rats after oral glucose tolerance and insulin tolerance tests, even though insulin signaling in skeletal muscles was decreased in the DHEA-treated group. CONCLUSION: DHEA-treated rats had reproductive abnormalities which mimicked symptoms of human PCOS. In metabolic parameters, DHEA treatment did not show insulin resistance in the female rats, suggesting that the use of DHEA-treated rats is not a good animal model for the study of metabolic abnormalities in PCOS.