Discovery of cycloheptapeptides phakefusins A-E from the marine sponge Phakellia fusca based on molecular networking.

Guided by a probe-based molecular networking strategy, five undescribed cycloheptapeptides, phakefusins A-E (1-5), were isolated from the marine sponge Phakellia fusca. Compounds 1 and 2 contain the nonproteinogenic amino acid residues of dioxindolyalanine (Dioia) and ß-3-oxindolylalanine (Oia), respectively. Compound 3 possesses a unique methionine sulfoxide, whereas compound 5 includes a glutamic acid ethyl ester unit. Their structures were elucidated through NMR spectroscopy, HR-MS/MS analysis, and the advanced Marfey's method. By synthesizing the (S, S/R)-Oia standard through tryptophan oxidation, we determined the configuration of this amino acid in compound 2 using the advanced Marfey's method. These cycloheptapeptides were evaluated for their antitumor, antibacterial, and antioxidant activities. Compound 1 showed moderate cytotoxicity against MCF-7 and PC9 cells, with IC50 values of 6.8 and 9.6 µM, respectively, while compounds 2-5 demonstrated potential antioxidant effects by upregulating HO-1, NQO1, and SOD2 levels, as well as inducing Nrf2 activation.

Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from Aaptos aaptos sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear. Our research indicates that AP-7 bolsters the growth inhibition activity of DDP on multidrug-resistant NSCLC cells. AP-7 notably disrupts DDP-induced cell cycle arrest and amplifies DDP-induced DNA damage effects in these cells. Furthermore, the combination of AP-7 and DDP downregulates Chk1 activation, interrupts the DNA damage repair-dependent Chk1/CDK1 pathway, and helps to overcome drug resistance and boost apoptosis in multidrug-resistant NSCLC cells and a gefitinib-resistant xenograft mice model. In summary, AP-7 appears to enhance DDP-induced DNA damage by impeding the Chk1 signaling pathway in multidrug-resistant NSCLC, thereby augmenting growth inhibition, both in vitro and in vivo. These results indicate the potential use of AP-7 as a DDP sensitizer in the treatment of multidrug-resistant NSCLC.

Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL. AP-48 is an aaptamine alkaloid analog with potent anti-tumor effects that originates from marine natural products. In this study, we found that AP-48 exhibits dose-dependent cytotoxicity in DLBCL cell lines. Flow cytometry showed that AP-48 induced cell cycle arrest in the G0/G1 phase in SU-DHL-4 and Farage cells and in the S phase in WSU-DLCL-2 cells. AP-48 also accelerated apoptosis via the caspase-3-mediated intrinsic apoptotic pathway. Further experiments demonstrated that AP-48 exerted its anti-DLBCL effects through the PI3K/AKT/mTOR pathway, and that the PI3K agonist YS49 partially alleviated the inhibition of cell proliferation and apoptosis induced by AP-48. Finally, in a tumor xenograft model, AP-48 inhibited tumor growth and promoted apoptosis in tumor tissues, indicating its therapeutic potential in DLBCL.

Marine derived macrolide bryostatin 4 inhibits the TGF-ß signaling pathway against acute erythroleukemia.

PURPOSE: Acute erythroleukemia (AEL) is a rare and highly aggressive subtype of acute myeloid leukemia (AML) with an extremely poor prognosis when treated with available drugs. Therefore, new investigational agents capable of inducing remission are urgently required. METHODS: Bioinformatics analysis, western blot and qRT-PCR were used to reveal the potential biological mechanism of bryostatin 4 (B4), an antineoplastic macrolide derived from the marine bryozoan Bugula neritina. Then, in vivo experiments were conducted to evaluate the role of transforming growth factor (TGF)-ß signaling in the progression of AEL. RESULTS: Our results revealed that the proliferation of K562 cells and TF-1 cells was significantly inhibited by B4 at IC50 values of 37 nM and 52 nM, respectively. B4 inhibited TGF-ß signaling and its downstream pathway targets, particularly the phosphorylation of Smad2, Smad3, Ras, C-RAF, ERK1/2, and MEK. B4 also played an important role in cell invasion and migration in K562 cells and TF-1 cells by reducing the protein levels of the mesenchymal cell marker vimentin. Moreover, Flow cytometry and western blot analyses demonstrated that B4 induced apoptosis and initiated G0/G1 phase arrest by modulating mitochondrial dysfunction and cyclin-dependent kinase (CDK) expression. CONCLUSION: These findings indicated that B4 could inhibit the proliferation, migration, invasion, and TGF-ß signaling pathways of AEL cells, thus suggesting that B4 possesses therapeutic potential as a treatment for AEL.

Isolation and absolute configuration of alkylpyridine alkaloids from the marine sponge Hippospongia lachne.

Marine sponges are well known as prolific producers of structurally diverse molecules with valuable pharmacological potential. As part of our ongoing program to discover bioactive compounds from marine sponges collected from the Xisha Islands in the South China Sea, a chemical study on the specimens of Hippospongia lachne was conducted. As a result, eight undescribed compounds, including four zwitterionic alkylpyridinium salts, hippospondines A-D (1-4), and four 3-alkylpyridine alkaloids, hippospondines E (5), F (6), and (±)-hippospondine G (7), were isolated from the marine sponge H. lachne, together with one known 3-alkylpyridine alkaloid (8). The undescribed structures were elucidated by HRESIMS, NMR, DP4+ and CP3 probability analysis, and the Snatzke's method. Hippospondines A-D (1-4) represent the rare example of inner salt type alkylpyridinium alkaloid with a farnesyl moiety. Compounds 1-3 and 8 were subjected to cytotoxic and lymphocyte proliferation assays. Compound 3 exhibited a weak promotion effect on the ConA-induced T lymphocyte proliferation.

Hipposponols A and B, two new 9, 11-secosterols from the marine sponge Hippospongia lachne de Laubenfels.

Two new 9,11-secosterols, hipposponols A (1) and B (2), together with five known analogues, aplidiasterol B (3), (3ß,5α,6ß)-3,5,6-triol-cholest-7-ene (4), (3ß,5α,6ß,22E)-3,5,6-triol-ergosta-7,22-diene (5), and one pair of inseparable C-24 epimers of (3ß,5α,6ß,22E)-3,5,6-triol-stigmasta-7,22-diene (6/7), were isolated from the marine sponge Hippospongia lachne de Laubenfels. The structures of isolated compounds were extensively elucidated based on HRESIMS and NMR data. Compounds 2 - 5 showed cytotoxicity against PC9 cells with IC50 values ranging from 34.1 ± 0.9 to 38.9 ± 1.0 µM and compound 4 displayed cytotoxicity against MCF-7 cells with IC50 value of 39.0 ± 0.4 µM.

Marine Sponge-Derived Alkaloid Induces Mitochondrial Dysfunction and Inhibits the PI3K/AKT/mTOR Signaling Pathway against Burkitt's Lymphoma.

Burkitt's lymphoma (BL) has a particularly extremely poor prognosis and the fastest growth rate among human tumors, and the development of new drugs for the treatment of BL is urgently needed. In this study, the cytotoxic properties of 3,7-bis(3,5-dimethylphenyl)-aaptamine (AP-51), a new semisynthetic alkaloid derived from the marine natural product aapatamine, were investigated using BL cell lines. Our results showed that AP-51 inhibited the proliferation of Daudi and Raji cells with IC50 values of 3.48 and 2.07 µM, respectively. Flow cytometry and Western blot analyses showed that AP-51 initiated G0/G1 phase arrest by modulating the expression of cyclin-dependent kinases (CDKs). AP-51 also induced apoptosis, as demonstrated by nuclear fragmentation, downregulation of BCL-XL and Mcl-1, and upregulation of cleaved caspase-9, cleaved caspase-3, cleaved-PARP, and cytochrome c, the markers of apoptosis regulated via the mitochondrial pathway. When it comes to mitochondria, AP-51 treatment also significantly increased the levels of intracellular mitochondrial superoxide, decreased ATP content, and reduced the expression of ATP synthase, as well as the expression of the mitochondrial respiratory chain complexes. Finally, AP-51 treatment significantly inhibited the PI3K/AKT/mTOR signaling pathway, which was shown to be associated with the induction of apoptosis. Collectively, these findings indicated that AP-51 initiated cell cycle arrest, induced apoptosis, caused mitochondrial dysfunction, and decreased the phosphorylation of PI3K/AKT/mTOR signaling pathway-related proteins and the protein levels of C-MYC, suggesting that AP-51 has therapeutic potential as a possible treatment for Burkitt's lymphoma.

Axinellasins A-D, Immunosuppressive Cycloheptapeptide Diastereomers, Discovered via a Precursor Ion Scanning-Supercritical Fluid Chromatography Strategy from the Marine Sponge Axinella species.

The precursor ion scanning-supercritical fluid chromatography (PI-SFC) method was applied to explore new methionine sulfoxide-containing cycloheptapeptides, axinellasins A-D (1-4), from the marine sponge Axinella sp. Their structures, including absolute configurations, were elucidated by detailed spectroscopic analyses and X-ray crystallography. The total synthesis of 4 was completed via an Fmoc solid/solution-phase synthesis. Compounds 1-4 exhibited immunosuppressive effects via inhibition of T and B cell proliferation, and 1 and 4 showed better inhibitory activities than their corresponding diastereomers.

Epidemiological characteristics, clinical characteristics, and prognostic factors of children with atopy hospitalised with adenovirus pneumonia.

BACKGROUND: Atopy may be associated with disease severity and a poor prognosis of human adenovirus (HAdV) pneumonia in children. Our aim was to observe the clinical characteristics and pulmonary radiological changes in children with atopy and HAdV pneumonia in China. METHODS: Children hospitalised with HAdV pneumonia from June 2018 to December 2019 were analysed. All children were divided into atopic with HAdV, non-atopic with HAdV, and atopic without HAdV infection group. Each group was further divided into the mild and severe pneumonia groups according to disease severity. Standard treatment was initiated after admission, and regular follow-up evaluations were conducted at 1 month after discharge. Baseline and clinical characteristics and pulmonary radiological changes in children with and without atopy were evaluated. Risk factors associated with small airway lesions in patients with HAdV pneumonia were analysed. RESULTS: The eosinophil count in the atopic group was significantly higher than that in the non-atopic group (P < 0.05). Severe coughing, wheezing, and small airway lesions on chest high-resolution computed tomography (HRCT) upon admission, after discharge and 1 month after discharge were significantly higher in the atopic group (with or without HAdV infection) than in the non-atopic group (P < 0.05). There were significant differences in the number of patients with wheezing and small airway lesions during hospitalisation and after discharge among the three groups (P < 0.05). The risks of small airway lesions in children with a family or personal history of asthma, severe infection, atopy, and HAdV infection were 2.1-, 2.7-, 1.9-, 2.1-, and 1.4-times higher than those in children without these characteristics, respectively. CONCLUSIONS: Children with atopy and HAdV pneumonia may experience severe coughing in mild cases and wheezing in mild and severe cases. Children with atopy are more susceptible to the development of small airway lesions, recurrent wheezing after discharge and slower recovery of small airway lesions as observed on pulmonary imaging than non-atopic children after HAdV infection. A family or personal history of asthma, atopy, severe infection, and HAdV infection are independent risk factors associated with the development of small airway lesion as observed on chest HRCT.

Dysiscalarones A-E, scalarane sesterterpenoids with nitric oxide production inhibitory activity from marine sponge Dysidea granulosa.

Dysiscalarones A-E (1-5), five new scalarane-type bishomoscalarane sesterterpenoids, were isolated from marine sponge Dysidea granulosa collected from the South China Sea, together with two known ones, honulactone A (6) and phyllofolactone I (7). The new structures were determined by extensive spectroscopic analysis including HR-ESI-MS and 1D and 2D NMR data, and their absolute configurations were assigned by single crystal X-ray diffraction analyses. The inhibitory activity of all the seven isolates on the production of nitric oxide (NO) stimulated by lipopolysaccharide (LPS) in mouse RAW 264.7 macrophages was evaluated. Of these metabolites, dysiscalarones A-B (1-2), honulactone A (6), and phyllofolactone I (7) showed inhibitory activities with respective IC50 values of 16.4, 18.5, 2.6, and 3.7 µM, which suggested that the γ-methylated α,ß-unsaturated γ-lactone might be the functional group. In addition, all the seven metabolites showed no significant cytotoxicity against lung cancer PC9 cell line at the concentration of 20 µM.

Phakefustatins A-C: Kynurenine-Bearing Cycloheptapeptides as RXRα Modulators from the Marine Sponge Phakellia fusca.

A neutral-loss scanning mass method was used to explore new kynurenine-containing cycloheptapeptides, phakefustatins A-C (1-3), from the marine sponge Phakellia fusca. Their structures were elucidated by spectroscopic analysis and the advanced Marfey's method. 1 was total synthesized via a final-stage ozonolysis strategy by the combination of solid/solution-phase synthesis. Phakefustatin A (1) was identified as a RXRα modulator to inhibit cancer cell growth, and its pharmacophores could be Kyn and guanidine groups.

Pseudoglandular myxoid adrenocortical adenoma with positive epithelial markers: a case report and review of the literature.

Myxoid adrenal cortical adenoma with a pseudoglandular structure is a special histological variant and is extremely rare. We report about a 32-year-old Chinese woman with a right adrenal mass during a routine physical examination. The cut surface of the mass had a vague nodular, which gross appearance was pale, yellowish, and semitransparent. Histologically, the region is mostly characterised by pseudoglandular pattern with myxoid stroma. They are filled with clear cells or eosinophilic cells, as well as semitransparent regions, in which anastomosing small eosinophilic cells arranged in pseudoglandular, cord-like, or wreath-shaped structure float in the mucous pool. Immunohistochemical staining shows Melan-A, vimentin, and CD56 were positive and CK (AE1/AE3) were nucleus-side staining. A small number of tumor cells were positive for alpha-inhibin and synaptophysin, ki-67 labeling index was 3%. EMA, chromogranin A, WT-1, and P63 were negative. This report aimed to emphasize pseudoglandular patterns with mucus secretion which could occur in adenomas of the adrenal cortex, nucleus-side positive for CK is remarkable. However, this type may have malignant potential, so regular follow-up is needed.

Cinerols, Nitrogenous Meroterpenoids from the Marine Sponge Dysidea cinerea.

Eleven new nitrogenous meroterpenoids, cinerols A-K (1-11), were isolated from the marine sponge Dysidea cinerea collected in the South China Sea, and their structures were determined by detailed spectroscopic analysis. Cinerols A (1) and B (2) feature a rare 5H-pyrrolo[1,2a]benzimidazole moiety, while cinerols C-G (3-7) are examples of rare meroterpene benzoxazoles. The cinerols are noncytotoxic to human melanoma A375 cells at the concentration of 32 µM; however, selected cinerols exhibit moderate inhibitory activity against one or more of protein-tyrosine phosphatase 1B, ATP-citrate lyase, and SH2 domain-containing phosphatase-1 with IC50 values of 2.8-27 µM.

Fuscasins A-D, Cycloheptapeptides from the Marine Sponge Phakellia fusca.

Four new cycloheptapeptides, fuscasins A-D (1-4), were isolated from the marine sponge Phakellia fusca collected from the South China Sea. Their planar structures were fully characterized by spectroscopic methods, and the absolute configurations of amino acid residues were determined using the advanced Marfey's method. Structurally, 1 is a unique cycloheptapeptide with a backbone bearing a pyrrolidine-2,5-dione unit. Among the isolated compounds, 1 exhibited potent growth-inhibitory activity against HepG2 cells with an IC50 value of 4.6 µM, whereas it did not show apparent inhibitory effects against the other five human cancer cell lines, MCF-7, HeLa, NCI-H460, PC9, and SW480. Encouragingly, 1 exhibited no cytotoxicity against nonmalignant cells even with a concentration up to 100 µM. These findings suggest that 1 may display a selective inhibitory effect on the growth of HepG2 cells.

Vasoactive intestinal peptide inhibits airway smooth muscle cell proliferation in a mouse model of asthma via the ERK1/2 signaling pathway.

Asthma is a heterogeneous clinical syndrome characterized by airway inflammation, hyper-responsiveness and remodeling. Airway remodeling is irreversible by current antiasthmatic drugs, and it is the main cause of severe asthma. Airway smooth muscle cells (ASMCs) act as the main effector cells for airway remodeling; the proliferation and hypertrophy of which are involved in airway remodeling. Caveolin (Cav)- 1 is present on the surface of ASMCs, which is involved in cell cycle and signal transduction regulation, allowing ASMCs to change from proliferation to apoptosis. The extracellular signal-regulated kinase (ERK)1/2 signaling pathway is a common pathway regulated by various proliferative factors, which demonstrates a regulatory role in airway remodeling of asthma. There have been many studies on the correlation between vasoactive intestinal peptide (VIP) and airway reactivity and inflammation in asthma, but the functions and related mechanisms of ASMCs remain unclear. In this study, we established an airway remodeling model in asthmatic mice, and concluded that VIP inhibits airway remodeling in vivo. The in vitro effect of VIP on interleukin-13-induced proliferation of ASMCs was studied by examining the effects of VIP on expression of ERK1/2, phospho-ERK1/2 and Cav-1 in ASMCs, as well as changes in cell cycle distribution. VIP inhibited phosphorylation of the ERK1/2 signaling pathway and expression of Cav-1 on ASMCs and decreased the proportion of S phase cells in the cell cycle, thus inhibiting the proliferation of ASMCs. This study provides a novel therapeutic mechanism for the treatment of asthma.

A case of matrix-producing carcinoma of the breast with micoglandular adenosis and review of literature.

Matrix-producing carcinoma (MPC) of the breast is an extremely rare variant of metaplastic breast carcinoma that contains a mixture of epithelial and mesenchymal elements. As overt carcinoma with direct transition to a cartilaginous and/or osseous stromal matrix cells, MPC is of no spindle cells between those two elements. This is the case of a 43 year-old female patient with MPC which coexisted with microglandular adenosis (MGA), atypical MGA (AMGA) and carcinoma in situ arising in MGA (MGACA in situ). MGA is a rare, infiltrative, benign lesion of the breast with an indolent clinical course. Histological evidence of carcinoma arising from MGA has previously been documented. MPC arising in MGA is an extremely rare subtype of breast carcinoma and has been seldom detailed described in the previous studies. This report highlights one such case with cytomorphological and histopathological correlation, along with a review of pertinent literature and differential diagnosis.

[Application of minimally invasive, decompression bone graft implantation combined with metal trabecular bone reconstruction system for early stage osteonecrosis of femoral head].

OBJECTIVE: To observe the application effect of minimally invasive decompression, bone graft implantation and metal trabecular bone reconstruction system for early stage osteonecrosis of femoral head and discuss the treatment of hip-salvage operation in early stage osteonecrosis of femoral head; METHODS: From January 2010 to June 2011, 50 patients (62 hips) Which were osteonecrosis of femoral head of early stake,were treated with minimally invasive decompression, bone graft implantation and metal trabecular bone reconstruction system, including 31 males (40 hips), 19 females (22 hip) with an average age of 36.2 years old ranging from 22 to 54 years old. The course of disease was from 6 to 15 months (averaged 10.5 months). Among them, 19 cases (23 hips) were steroid-induced, 25 cases (33 hips) were alcohol-induced, 6 cases (6 hips) were idiopathic; According to ARCO stage, 28 hips were at stage I, 34 hips were at stage II. All of them were diagnosed as femoral head necrosis by imaging examination before operation. Then each patient was followed to assess by Harris hip score, curative effect, and conduct the femoral head survival analysis during the postoperation. RESULTS: All patients had finished operation, the operation time was between 30 and 85 min, intraoperative blood loss was 50 to 220 ml, and 47 cases (58 hips) were follow-up from 24 to 46 months with an average of 34.05 months. As compared with preoperative, the Harris hip score at the last follow-up was improved, the difference was statistically significant (P<0.01). The Harris hip score, curative effect and survival time of femoral head in ARCO stage I was superior to these in ARCO Stage II, the difference was statistically significant (P< 0.05). CONCLUSION: Effect of minimally invasive decompression,bone graft implantation combine with the metal trabecular bone reconstruction system for early stage osteonecrosis of femoral head was good,it could significantly improve the Harris hip score, increase the femoral head survival time, delay the hip replacement, and performance better in ARCO stage I.

Expression and prognostic significance of VEGFR-2 in breast cancer.

Breast cancer is one of the most common cancers among women in the world. Vascular endothelial growth factor receptor 2 (VEGFR-2) was not only found to play a key role in the development of tumor angiogenesis, but has also been located in tumor cells of a variety of tumors. This study investigated the expression pattern of VEGFR-2 in breast cancer tissue specimens in order to evaluate the role of VEGFR-2 in the prognosis of breast cancer. Expression and localization of VEGFR-2 in tumor cells of breast cancer specimens from 98 invasive breast cancer patients were determined by immunohistochemistry. The relationships between VEGFR-2 expression and clinicopathological features were also analyzed. The results showed that VEGFR-2 expression correlated positively with lymph node (LN) metastasis of breast cancer. Patients with high expression of VEGFR-2 had a significantly worse OS. It was also observed that the expression of epithelial-mesenchymal transition (EMT) marker, including Twist1 and Vimentin, was higher in the tumors with higher VEGFR-2 expression, while the E-cadherin expression was lower in the same tumors, suggesting that VEGFR-2 may serve as a possible mediator of EMT in breast cancer.

Serum amyloid A protein: a potential biomarker correlated with clinical stage of lung cancer.

OBJECTIVE: To identify serum diagnosis or progression biomarkers in patients with lung cancer using protein chip profiling analysis. METHOD: Profiling analysis was performed on 450 sera collected from 213 patients with lung cancer, 19 with pneumonia, 16 with pulmonary tuberculosis, 65 with laryngeal carcinoma, 55 with laryngopharyngeal carcinoma patients, and 82 normal individuals. A new strategy was developed to identify the biomarkers on chip by trypsin pre-digestion. RESULTS: Profiling analysis demonstrated that an 11.6 kDa protein was significantly elevated in lung cancer patients, compared with the control groups (P < 0.001). The level and percentage of 11.6 kDa protein progressively increased with the clinical stages I-IV and were also higher in patients with squamous cell carcinoma than in other subtypes. This biomarker could be decreased after operation or chemotherapy. On the other hand, 11.6 kDa protein was also increased in 50% benign diseases of lung and 13% of other cancer controls. After trypsin pre-digestion, a set of new peptide biomarkers was noticed to appear only in the samples containing a 11.6 kDa peak. Further identification showed that 2177 Da was a fragment of serum amyloid A (SAA, MW 11.6 kDa). Two of the new peaks, 1550 Da and 1611 Da, were defined from the same protein by database searching. This result was further confirmed by partial purification of 11.6 kDa protein and MS analysis. CONCLUSION: SAA is a useful biomarker to monitor the progression of lung cancer and can directly identify some biomarkers on chip.

Estrogenic effect of yam ingestion in healthy postmenopausal women.

OBJECTIVE: Yam (Dioscorea) has been used to treat menopausal symptom folklorically. This study was to investigate the effects of yam ingestion on lipids, antioxidant status, and sex hormones in postmenopausal women. METHODS: Twenty-four apparently healthy postmenopausal women were recruited to replace their staple food (rice for the most part) with 390 g of yam (Dioscorea alata) in 2 of 3 meals per day for 30 days and 22 completed the study. Fasting blood and first morning urine samples were collected before and after yam intervention for the analyses of blood lipids, sex hormones, urinary estrogen metabolites and oxidant stress biomarker. The design was a one arm, pre-post study. A similar study of postmenopausal women (n = 19) fed 240 g of sweet potato for 41 days was included as a control study. Serum levels of estrone, estradiol and SHBG were analyzed for this control group. RESULTS: After yam ingestion, there were significant increases in serum concentrations of estrone (26%), sex hormone binding globulin (SHBG) (9.5%), and near significant increase in estradiol (27%). No significant changes were observed in serum concentrations of dehydroepiandrosterone sulfate, androstenedione, testosterone, follicular stimulating hormone, and luteinizing hormone. Free androgen index estimated from the ratio of serum concentrations of total testosterone to SHBG decreased. Urinary concentrations of the genotoxic metabolite of estrogen, 16alpha-hydroxyestrone decreased significantly by 37%. Plasma cholesterol concentration decreased significantly by 5.9%. Lag time of low-density lipoprotein oxidation prolonged significantly by 5.8% and urinary isoprostane levels decreased significantly by 42%. For the control subjects fed with sweet potato, all three hormone parameters measured were not changed after intervention. CONCLUSION: Although the exact mechanism is not clear, replacing two thirds of staple food with yam for 30 days improves the status of sex hormones, lipids, and antioxidants. These effects might reduce the risk of breast cancer and cardiovascular diseases in postmenopausal women.