Dual-modified starch micelles as nanocarriers for efficient encapsulation and controlled release of walnut-derived active peptides.

Hydrophilic and hydrophobic modified nanomicelles might be more conducive to passage of the gastrointestinal barrier than walnut peptide (WP). In this study, a novel double modified starch polymer, SB-CST-DCA, was synthesized by grafting sulfabetaine (SB) and deoxycholic acid (DCA) onto corn starch (CST) molecules through etherification and esterification. The modification mechanism was discussed to determine its chemical structure, morphological properties, and thermal stability. Peptide-loaded nanomicelles (SB-CST-DCA-WP) were prepared using WP as the core material. The encapsulation efficiency and peptide loading amount reached 76.90 ± 1.52% and 18.27 ± 0.53%, respectively, with good stability and pH-responsive release behavior observed to effectively control WP release and enhance its antioxidant activity. The composite exhibited safety, non-toxicity, and good blood compatibility at concentrations below 125 µg/mL. Duodenum was identified as the main absorption site with an absorption ratio of 41.16 ± 0.36%.

Novel strategy to the characterization and enhance the glycemic control properties of walnut-derived peptides via zinc chelation.

This study aimed to utilize zinc coordination to promote the hypoglycemic and antioxidant properties of walnut-derived peptides, such as walnut protein hydrolysate (WPH) and Leu-Pro-Leu-Leu-Arg (LPLLR, LP5), of which LP5 was previously identified from WPH. The optimal conditions for the chelation were a peptide-to-zinc ratio of 6:1, pH of 9, duration of 50 min, and temperature of 50 °C. The WPH-Zn and LP5-Zn complexes increased the α-glucosidase inhibition, α-amylase inhibition, and antioxidant activity more than WPH and LP5 (p < 0.05). In particular, the antioxidant activity of WPH-Zn was superior to LP5-Zn. This is attributable to the WPH containing more aromatic amino acids, carboxylate groups and the imidazole groups, which implies its capacity to potentially coordinate with Zn2+ to form the WPH-Zn complex. Moreover, particle size, zeta potential, and scanning electron microscope indicated that the chelation of Zn2+ by peptides led to intramolecular and intermolecular folding and aggregation.

Lagging effects and prediction of pollutants and their interaction modifiers on influenza in northeastern China.

BACKGROUND: Previous studies have typically explored the daily lagged relations between influenza and meteorology, but few have explored seasonally the monthly lagged relationship, interaction and multiple prediction between influenza and pollution. Our specific objectives are to evaluate the lagged and interaction effects of pollution factors and construct models for estimating influenza incidence in a hierarchical manner. METHODS: Our researchers collect influenza case data from 2005 to 2018 with meteorological and contaminative factors in Northeast China. We develop a generalized additive model with up to 6 months of maximum lag to analyze the impact of pollution factors on influenza cases and their interaction effects. We employ LASSO regression to identify the most significant environmental factors and conduct multiple complex regression analysis. In addition, quantile regression is taken to model the relation between influenza morbidity and specific percentiles (or quantiles) of meteorological factors. RESULTS: The influenza epidemic in Northeast China has shown an upward trend year by year. The excessive incidence of influenza in Northeast China may be attributed to the suspected primary air pollutant, NO2, which has been observed to have overall low levels during January, March, and June. The Age 15-24 group shows an increase in the relative risk of influenza with an increase in PM2.5 concentration, with a lag of 0-6 months (ERR 1.08, 95% CI 0.10-2.07). In the quantitative analysis of the interaction model, PM10 at the level of 100-120 µg/m3, PM2.5 at the level of 60-80 µg/m3, and NO2 at the level of 60 µg/m3 or more have the greatest effect on the onset of influenza. The GPR model behaves better among prediction models. CONCLUSIONS: Exposure to the air pollutant NO2 is associated with an increased risk of influenza with a cumulative lag effect. Prioritizing winter and spring pollution monitoring and influenza prediction modeling should be our focus.

Purification, Identification, Chelation Mechanism, and Calcium Absorption Activity of a Novel Calcium-Binding Peptide from Peanut (Arachis hypogaea) Protein Hydrolysate.

A novel calcium-binding peptide was purified from peanut protein hydrolysate using gel filtration chromatography and identified using HPLC-MS/MS. Its amino acid sequence was determined as Phe-Pro-Pro-Asp-Val-Ala (FPPDVA, named as FA6) with the calcium-binding capacity of 15.67 ± 0.39 mg/g. Then, the calcium chelating characteristics of FPPDVA were investigated using ultraviolet-visible absorption spectroscopy, fluorescence spectroscopy, Fourier transform infrared spectroscopy, particle size, and zeta potential. The results showed that FPPDVA interacted with calcium ions, the chelation of calcium ions induced FPPDVA to fold and form a denser structure, the calcium-binding sites may mainly involve oxygen atoms from the carboxyl residues of Asp and Ala, and Phe possessed contact energy and carbonyl residues of Val. Microstructure analysis showed that FPPDVA-calcium chelate exhibited a regularly ordered and tightly aggregated sheets or block structures. Additionally, FPPDVA-calcium chelate had good gastrointestinal digestive stability and thermal stability. The results of everted rat intestinal sac and Caco-2 cell monolayer experiments showed that FPPDVA-calcium chelate could promote calcium absorption and transport through the Cav1.3 and TRPV6 calcium channels. These data suggest that FPPDVA-calcium chelate possesses the potential to be developed and applied as calcium supplement.

A Unified Therapeutic-Prophylactic Tissue-Engineering Scaffold Demonstrated to Prevent Tumor Recurrence and Overcoming Infection toward Bone Remodeling.

Osteosarcoma occurs in children and adolescents frequently and leads to a high fatality rate. Although surgical resection is the most common methods in clinic, patients always suffer from tumor metastasis and recurrence and it is difficult for them to self-repair large bone defects. Furthermore, the postoperative infection from bacteria triggers an inflammatory response and hinders the bone-repair process. This work demonstrates a gadolinium (Gd)-complex and molybdenum sulfide (MoS2 ) co-doped N-acryloyl glycinamide (NAGA)/gelatin methacrylate (Gel-MA) multifunctional hydrogel (GMNG). The combination between NAGA and Gel-MA endows the GMNG with attractive mechanical properties and controllable degradation ability. The MoS2 improves the hydrogel system, which has excellent photothermal ability to kill tumor cells and inhibit bacterial infection both in vitro and in vivo. Based on the Gd-complex, the magnetic resonance imaging (MRI) effect can be used to monitor the position and degradation situation of the hydrogel. Notably, accompanied by the degradation of GMNG hydrogel, the gradually released Gd3+ from the hydrogel exhibits osteogenic property and could promote new bone formation efficiently in vivo. Therefore, this strategy supplies a method to prepare multifunctional bone-defect-repair materials and is expected to represent a significant guidance and reference to the development of biomaterials for bone tissue engineering.

Walnut-Derived Peptides Promote Autophagy via the Activation of AMPK/mTOR/ULK1 Pathway to Ameliorate Hyperglycemia in Type 2 Diabetic Mice.

Autophagy flux plays a significant protective role in type 2 diabetes mellitus (T2DM). However, the mechanisms by which autophagy mediates insulin resistance (IR) to ameliorate T2DM remain unclear. This study explored the hypoglycemic effects and mechanisms of walnut-derived peptides (fraction 3-10 kDa and LP5) in streptozotocin and high-fat-diet-induced T2DM mice. Findings revealed that walnut-derived peptides reduced the levels of blood glucose and FINS and ameliorated IR and dyslipidemia. They also increased SOD and GSH-PX activities and inhibited the secretion of TNF-α, IL-6, and IL-1ß. Additionally, they increased the levels of ATP, COX, SDH, and MMP of liver mitochondria. Western blotting indicated that walnut-derived peptides up-regulated LC3-II/LC3-I and Beclin-1 expression, while they down-regulated p62 expression, which may be associated with the activation of the AMPK/mTOR/ULK1 pathway. Finally, the AMPK activator (AICAR) and inhibitor (Compound C) were used to verify that LP5 could activate autophagy through the AMPK/mTOR/ULK1 pathway in IR HepG2 cells.

Distal tibial tubercle osteotomy can lessen change in patellar height post medial opening wedge high tibial osteotomy? A systematic review and meta-analysis.

OBJECTIVE: Medial opening wedge high tibial osteotomy (MOWHTO) is a mainstream surgical method for treating early medial compartment knee osteoarthritis. Undesirable sequelae such as patella infera may happen following tuberosity osteotomy. We conducted this systematic review and meta-analysis to compare the change in patellar position after proximal tibial tubercle osteotomy (PTO) versus distal tibial tubercle osteotomy (DTO) intervention. METHODS: The 11 studies were acquired from PubMed, Medline, Embase and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan5.3. Mean differences, odds ratios and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eleven observational studies were assessed. The methodological quality of the trials ranged from moderate to high. The pooled results of postoperative patellar height (Caton-Deschamps index and Blackburne-Peel index) and postoperative complications showed that the differences were statistically significant between PTO and DTO interventions. Patellar index ratios decreased significantly in the PTO groups, and 12 (9.2%) complications under DTO surgery and 2 (1.6%) complications under PTO surgery were reported. The differences of postoperative posterior tibial slope (angle) was not statistically significant, but postoperative posterior tibial slope of both groups increased. Sensitivity analysis proved the stability of the pooled results and the publication bias was not apparent. CONCLUSIONS: DTO in MOWHTO maintained the postoperative patellar height, and clinically, for patients with serious patellofemoral osteoarthritis, DTO can be preferred. Postoperative complications are easily preventable with caution. In view of the heterogeneity and small sample size, whether these conclusions are applicable should be further determined in future studies.

mRNA and long non-coding RNA expression profiles of rotator cuff tear patients reveal inflammatory features in long head of biceps tendon.

BACKGROUND: This study aimed to identify the differentially expressed mRNAs and lncRNAs in inflammatory long head of biceps tendon (LHBT) of rotator cuff tear (RCT) patients and further explore the function and potential targets of differentially expressed lncRNAs in biceps tendon pathology. METHODS: Human gene expression microarray was made between 3 inflammatory LHBT samples and 3 normal LHBT samples from RCT patients. GO analysis and KEGG pathway analysis were performed to annotate the function of differentially expressed mRNAs. The real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was admitted to verify their expression. LncRNA-mRNA co-expression network, cis-acting element, trans-acting element and transcription factor (TF) regulation analysis were constructed to predict the potential molecular regulatory mechanisms and targets for LHB tendinitis. RESULTS: 103 differentially expressed lncRNAs and mRNAs, of which 75 were up-regulated and 28 were down-regulated, were detected to be differentially expressed in LHBT. The expressions of 4 most differentially expressed lncRNAs (A2MP1, LOC100996671, COL6A4P, lnc-LRCH1-5) were confirmed by qRT-PCR. GO functional analysis indicated that related lncRNAs and mRNAs were involved in the biological processes of regulation of innate immune response, neutrophil chemotaxis, interleukin-1 cell response and others. KEGG pathway analysis indicated that related lncRNAs and mRNAs were involved in MAPK signaling pathway, NF-kappa B signaling pathway, cAMP signaling pathway and others. TF regulation analysis revealed that COL6A4P2, A2MP1 and LOC100996671 target NFKB2. CONCLUSIONS: LlncRNA-COL6A4P2, A2MP1 and LOC100996671 may regulate the inflammation of LHBT in RCT patients through NFKB2/NF-kappa B signaling pathway, and preliminarily revealed the pathological molecular mechanism of tendinitis of LHBT.

Was femoral nerve block effective for pain control of medial opening-wedge high tibial osteotomy?: A single blinded randomized controlled study.

BACKGROUND AND PURPOSE: Medial compartment femoro-tibial osteoarthritis (OA) is a common disease and opening-wedge high tibial osteotomy (OWHTO) is the common surgical procedure carried out for these patients. While most researchers are focusing on the surgical techniques during operation, the aim of this study is to evaluate the pain control effect of femoral nerve block (FNB) for OWHTO patients. METHODS: In this prospective, single-center, randomized controlled trial (RCT) study, 41 patients were operated on by OWHTO for OA during 2017 to 2018. Twenty of them (group A) accepted epidural anesthesia with FNB and 21 patients (group B) only had their single epidural anesthesia. All blocks were successful and all the 41 patients recruited were included in the analysis and there was no loss to follow-up or withdrawal. Systematic records of visual analog scores (VAS), quadriceps strength, mean number of times of patient-controlled intravenous analgesia (PCIA), using of additional opioids or nonsteroidal anti-inflammatory drugs (NSAIDs), and complications were done after hospitalization. The Student t test and Chi-Squared test was used and all P values ≤.05 were considered statistically significant. RESULTS: VAS scores at rest (3.48 ±â€Š1.0 vs 4.68 ±â€Š1.1) and on movemment (4.51 ±â€Š0.6 vs 4.97 ±â€Š0.8) decreased more in group A than group B with significance at follow-up of 12 hours. The quadriceps strength, consumption of additional opioids or NSAID injections and mean number of times that the patients pushed the PCIA button didnot differ significantly within each group. CONCLUSION: This RCT study shows that FNB in patients undergoing OWHTO for unicompartmental osteoarthritis of the knee could result in significant reduction in VAS scores at 12 hours postoperatively.Research registry, Researchregistry4792. Registered April 7, 2019 - Retrospectively registered, http://www.researchregistry.com.

Vitamin D3 protects articular cartilage by inhibiting the Wnt/ß-catenin signaling pathway.

Low expression levels of 25-hydroxyvitamin D (vitamin D3) in the blood have been reported to be associated with the progression of osteoarthritis; however, the mechanisms by which this occurs remain unclear. The present study aimed to determine the effects of vitamin D3 on chondrocytes. MTT assays were used to determine whether vitamin D3 affects chondrocytes viability. Primary chondrocytes were treated with control culture medium, vitamin D3, tumor necrosis factor (TNF)-α, TNF-α + PNU-74654 [Wingless-related integration site (Wnt)/ß-catenin signaling pathway inhibitor] or TNF-α + vitamin D3. Reverse transcription-quantitative PCR and western blotting were utilized to measure the gene and protein expression of collagen II, aggrecan, matrix metalloproteinase (MMP)-3 and MMP-13, A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS)-4, ADAMTS-5, Wnt-3a and nuclear ß-catenin. The results demonstrated that TNF-α reduced the expression levels of aggrecan and collagen II, and increased the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5. Furthermore, vitamin D3 and PNU-74654 were observed to partially attenuate the effects induced by TNF-α. Moreover, similar findings were reported following co-treatment with vitamin D3 and TNF-α. Western blotting data revealed that TNF-α increased Wnt-3a and ß-catenin protein levels in chondrocytes, while Vitamin D3 and PNU-74654 decreased the expression levels of Wnt-3a and nuclear ß-catenin. In conclusion, the findings of the present study provided evidence to suggest that vitamin D3 may prevent articular cartilage degeneration and osteoarthritic disease progression by inhibiting the expression levels of MMP-3, MMP-13, ADAMTS-4 and ADAMTS-5 through suppressing the Wnt/ß-catenin signaling pathway. These results suggested that vitamin D3 may be of therapeutic value for the prevention and treatment of osteoarthritis.

Opening-Wedge High Tibial Osteotomy Using Autograft versus Allograft: A Systematic Review and Meta-analysis.

Bone grafting is a good alternative for filling the inevitable void that is created following opening-wedge high tibial osteotomy (OWHTO). This systematic review and meta-analysis evaluated whether bone grafting is necessary for OWHTO and the successful outcomes of OWHTO using either autograft (AU) or allograft (AL). All analyzed studies were acquired from PubMed, Medline, Embase, CNKI, Google Scholar, and Cochrane Library. Data were independently extracted by two coauthors and were analyzed using RevMan5.3. Mean differences, odds ratios, and 95% confidence intervals were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess the risk of bias. In total, 10 studies were assessed including three randomized controlled trials and seven observational studies. The methodological quality of the trials ranged from low to high. The overall estimate demonstrated that the difference between OWHTO using AU and AL groups and OWHTO using no filling group was not statistically significant for the loss of correction, and complications, but OWHTO using no filling group statistically showed better knee society score. Pooled results of reoperations, lateral cortex breaches, complications, and clinical function assessments showed no significant difference between AU and AL materials. Using AL statistically reduced the operative time compared with using AU. OWHTO with or without bone graft does not affect postoperative complications. No loss of correction was observed due to the lack of bone grafting. In addition, OWHTO without bone graft performs better for postoperative clinical function assessment. Complications and clinical results of medial OWHTO were similar using AL and AU and neither reported a median loss of correction of following OWHTO. Compared with using AU, using AL avoids harvest site complications and reduces operative time. To sum up, OWHTO without any bone graft is recommended for medial unicompartmental osteoarthritis of the knee. Further large-sample, multicenter, high-quality, randomized controlled trials are warranted to verify the outcomes of this meta-analysis.

Is arthroscopic repair superior to biceps tenotomy and tenodesis for type II SLAP lesions? A meta-analysis of RCTs and observational studies.

OBJECTIVE: Labral repair and biceps tenotomy and tenodesis are routine operations for type II superior labrum anterior posterior (SLAP) lesion of the shoulder, but evidence of their superiority is lacking. We conducted this systematic review and meta-analysis to compare the clinical outcomes of arthroscopic repair versus biceps tenotomy and tenodesis intervention. METHODS: The eight studies were acquired from PubMed, Medline, Embase, CNKI, and Cochrane Library. The data were extracted by two of the coauthors independently and were analyzed by RevMan 5.3. Mean differences (MDs), odds ratios (ORs), and 95% confidence intervals (CIs) were calculated. Cochrane Collaboration's Risk of Bias Tool and Newcastle-Ottawa Scale were used to assess risk of bias. RESULTS: Eight studies including two randomized controlled trials (RCTs) and six observational studies were assessed. The methodological quality of the trials ranged from low to moderate. The pooled results of UCLA score, SST score, and complications showed that the differences were not statistically significant between the two interventions. The difference of ASES score and satisfaction rate was statistically significant between arthroscopic repair and biceps tenotomy and tenodesis intervention, and arthroscopic biceps tenotomy and tenodesis treatment was more effective. Sensitivity analysis proved the stability of the pooled results, and there were too less included articles to verify the publication bias. CONCLUSIONS: Both arthroscopic repair and biceps tenotomy and tenodesis interventions had benefits in type II SLAP lesions. Arthroscopic biceps tenotomy and tenodesis treatment provides better clinical outcome in ASES score and satisfaction rate and comparable complications compared with arthroscopic repair treatment. In view of the heterogeneity and confounding factors, whether these conclusions are applicable should be further determined in future studies.

Sphingosine-1-phosphate mediates the therapeutic effects of bone marrow mesenchymal stem cell-derived microvesicles on articular cartilage defect.

Microvesicles (MVs) are emerging as a new mechanism of intercellular communication by transferring cellular components to target cells, yet their function in disease is just being explored. However, the therapeutic effects of MVs in cartilage injury and degeneration remain unknown. We found MVs contained high levels of sphingosine-1-phosphate (S1P) compared with the original bone marrow mesenchymal stem cells (MSCs). The enrichment of S1P in MVs was mediated by sphingosine kinase 1 (SphK1), but not by sphingosine kinase 2 (SphK2). Co-culture of human chondrocytes with MVs resulted in increased proliferation of chondrocytes in vitro, which was mediated by activation of S1P receptor 1 (S1PR1) expressed on chondrocytes. Meanwhile, MVs inhibited interleukin 1 beta-induced human chondrocytes apoptosis in a dose dependent manner. Furthermore, uptake of MVs by primary cultures of human chondrocytes was mediated by CD44 expressed by MVs. Anti-CD44 antibody significantly reduced the uptake of fluorescent protein-labeled MVs by chondrocytes. Further, blocking S1P by its neutralizing antibody significantly inhibited the therapeutic effects of MVs in vivo. Taken together, MVs showed therapeutic potential for treatment of clinical cartilage injury. This therapeutic potential is due to CD44-mediated uptake of MVs by chondrocytes and the S1P/S1PR1 axis-mediated proliferative effects of MVs on chondrocytes.

Zuotai and HgS differ from HgCl2 and methyl mercury in Hg accumulation and toxicity in weanling and aged rats.

Mercury sulfides are used in Ayurvedic medicines, Tibetan medicines, and Chinese medicines for thousands of years and are still used today. Cinnabar (α-HgS) and metacinnabar (ß-HgS) are different from mercury chloride (HgCl2) and methylmercury (MeHg) in their disposition and toxicity. Whether such scenario applies to weanling and aged animals is not known. To address this question, weanling (21d) and aged (450d) rats were orally given Zuotai (54% ß-HgS, 30mg/kg), HgS (α-HgS, 30mg/kg), HgCl2 (34.6mg/kg), or MeHg (MeHgCl, 3.2mg/kg) for 7days. Accumulation of Hg in kidney and liver, and the toxicity-sensitive gene expressions were examined. Animal body weight gain was decreased by HgCl2 and to a lesser extent by MeHg, but unaltered after Zuotai and HgS. HgCl2 and MeHg produced dramatic tissue Hg accumulation, increased kidney (kim-1 and Ngal) and liver (Ho-1) injury-sensitive gene expressions, but such changes are absent or mild after Zuotai and HgS. Aged rats were more susceptible than weanling rats to Hg toxicity. To examine roles of transporters in Hg accumulation, transporter gene expressions were examined. The expression of renal uptake transporters Oat1, Oct2, and Oatp4c1 and hepatic Oatp2 was decreased, while the expression of renal efflux transporter Mrp2, Mrp4 and Mdr1b was increased following HgCl2 and MeHg, but unaffected by Zuotai and HgS. Thus, Zuotai and HgS differ from HgCl2 and MeHg in producing tissue Hg accumulation and toxicity, and aged rats are more susceptible than weanling rats. Transporter expression could be adaptive means to reduce tissue Hg burden.

Ontogeny, aging, and gender-related changes in hepatic multidrug resistant protein genes in rats.

Multidrug resistance proteins (Mrps) are efflux transporters playing important roles in endogenous substances and xenobiotics transport out of the liver. Children, elderly, gender and physio-pathological conditions could influence their expression and result in changes in drug disposition. AIM: This study was aimed to examine the development-, aging-, and sex-dependent changes in Mrp1-4 and ATP-binding cassette sub-family G member 2 (Abcg2) gene expressions in livers of rats. MAIN METHODS: The livers from male and female SD rats at development (-2, 1,7,14,21,28,35, and 60d) and aging (28, 60, 180 and 540d) were collected and total RNA was isolated, purified and subjected to real-time RT-PCR analysis. KEY FINDINGS: Results showed that expression of Mrp1 was low, while Abcg2 and Mrp2 were the high in the liver. Mrp1 expression decreased with maturity but remained constant to 540d, while Mrp3 and 4 increased with liver development, reached the peak with maturity at 35-60days of age, and slightly reduced with aging. Mrp2 and Abcg2 were high at 7days of age and maintained at relative high levels till maturity, while Abcg2 was reduced during aging. Females had higher Mrp3 and Abcg2 mRNA expression than male rats, while male rats had higher Mrp2 and Mrp4 mRNA expression. SIGNIFICANCE: The expression of hepatic Mrp1-4 and Abcg2 mRNA during development, aging in male and female rats was characterized, which could be fundamental to our understanding of age- and sex-associated variations in drug disposition in children, elderly, and women.

Age- and sex-related differences of organic anion-transporting polypeptide gene expression in livers of rats.

Organic anion-transporting polypeptides (Oatps) play important roles in transporting endogenous substances and xenobiotics into the liver and are implicated in drug-drug interactions. Many factors could influence their expression and result in alterations in drug disposition, efficacy and toxicity. This study was aimed to examine the development-, aging-, and sex-dependent Oatps expression in livers of rats. The livers from SD rats during development (-2, 1, 7, 14, 21, 28, 35, and 60 d) and aging (60, 180, 540 and/or 800 d) were collected and total RNAs were extracted, purified, and subjected to real-time PCR analysis. Total proteins were extracted for western-blot analysis. Results showed that Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 were all hardly detectable in fetal rat livers, low at birth, rapidly increased after weaning (21 d), and reached the peak at 60 d. The Oatps remained stable during the age between 60-180 d, and decreased at elderly (540 and/or 800 d). After birth, Oatp1a1, Oatp1a4, and Oatp1b2 were all highly expressed in liver, in contrast, Oatp1a5 expression was low. Oatp expressions are male-predominant in rat livers. In the livers of aged rats, the Oatp expression decreased and shared a consistent ontogeny pattern at the mRNA and protein level. In conclusion, this study showed that in rat liver, Oatp1a1, Oatp1a4, Oatp1a5 and Oatp1b2 gene expressions are influenced by age and gender, which could provide a basis of individual variation in drug transport, metabolism and toxicity in children, elderly and women.