Comprehensive genomic analysis of the DUF4228 gene family in land plants and expression profiling of ATDUF4228 under abiotic stresses.

BACKGROUND: Domain of unknown function (DUF) proteins represent a number of gene families that encode functionally uncharacterized proteins in eukaryotes. The DUF4228 gene family is one of these families in plants that has not been described previously. RESULTS: In this study, we performed an extensive comparative analysis of DUF4228 proteins and determined their phylogeny in the plant lineage. A total of 489 high-confidence DUF4228 family members were identified from 14 land plant species, which sub-divided into three distinct phylogenetic groups: group I, group II and group III. A highly conserved DUF4228 domain and motif distribution existed in each group, implying their functional conservation. To reveal the possible biological functions of these DUF4228 genes, 25 ATDUF4228 sequences from Arabidopsis thaliana were selected for further analysis of characteristics such as their chromosomal position, gene duplications and gene structures. Ka/Ks analysis identified seven segmental duplication events, while no tandemly duplication gene pairs were found in A. thaliana. Some cis-elements responding to abiotic stress and phytohormones were identified in the upstream sequences of the ATDUF4228 genes. Expression profiling of the ATDUF4228 genes under abiotic stresses (mainly osmotic, salt and cold) and protein-protein interaction prediction suggested that some ATDUF4228 genes are may be involved in the pathways of plant resistance to abiotic stresses. CONCLUSION: These results expand our knowledge of the evolution of the DUF4228 gene family in plants and will contribute to the elucidation of the biological functions of DUF4228 genes in the future.

Practice effects of personalized interventions with interdisciplinary teamwork in type 2 diabetes remission: a retrospective study.

Objectives: A retrospective analysis of the clinical outcomes of personalized interventions for type 2 diabetes mellitus (T2DM) in an interdisciplinary team. Methods: Under the guidance of an interdisciplinary team, 40 patients with T2DM underwent a systematic examination at the beginning of the intervention, 3 months after the intervention, and 3 months of follow-up at the end of the intervention (i.e., at 6 months). Key indicators such as fasting plasma glucose (FPG), 2-hour postprandial glucose (2hPG), fasting insulin level (FINS), glycated hemoglobin (HbA1c), blood lipids, and body mass index (BMI) were measured. Results: After the 3-month intervention, participants' BMI, FPG, 2hPG, FINS, and HbA1c improved significantly, with statistically significant differences (P<0.05).These metrics remained essentially stable at the 3-month follow-up. Of all the participants, 92.5% (37 cases in total) successfully discontinued their medication after 3 months of intervention, of which 80% (32 cases) remained stable during the 3-month follow-up after discontinuation, fulfilling the criteria for remission of T2DM; 2 cases successfully reduced the dose of their medication, and only 1 case was maintained on the original treatment. Conclusions: Through an interdisciplinary team intervention strategy, we significantly optimized the glucose metabolism, lipid metabolism, and BMI status of patients with T2DM, making diabetes remission an achievable goal, which provides valuable experience for further optimization of diabetes prevention and control protocols.

Glucose addition and oven-heating of pork stimulate glycoxidation and protein carbonylation, while reducing lipid oxidation during simulated gastrointestinal digestion.

In the present study, it was investigated if glucose addition (3 or 5%) to pork stimulates glycoxidation (pentosidine, PEN), glycation (Maillard reaction products, MRP), lipid oxidation (4-hydroxy-2-nonenal, 4-HNE; hexanal, HEX; thiobarbituric acid reactive substances, TBARS), and protein oxidation (protein carbonyl compounds, PCC) during various heating conditions and subsequent in vitro gastrointestinal digestion. An increase in protein-bound PEN level was observed during meat digestion, which was significantly stimulated by glucose addition (up to 3.3-fold) and longer oven-heating time (up to 2.5-fold) of the meat. These changes were accompanied by the distinct formation of MRP during heating and digestion of the meats. Remarkably, stimulated glyc(oxid)ation was accompanied by increased protein oxidation, whereas lipid oxidation was decreased, indicating these reactions are interrelated during gastrointestinal digestion of meat. Glucose addition generally didn't affect these oxidative reactions when pork was packed preventing air exposure and oven-heated until a core temperature of 75 °C was reached.

Efficacy and safety of magnetic resonance-guided focused ultrasound for the treatment of osteoid osteoma: A systematic review and meta-analysis.

OBJECTIVE: Magnetic resonance-guided focused ultrasound (MRgFUS) is a novel noninvasive interventional technique for osteoid osteoma (OO). The purpose of this study was to evaluate the efficacy and safety of MRgFUS in the treatment of OO through a systematic review and meta-analysis of pain scores and post-treatment adverse events before and after MRgFUS treatment. MATERIALS AND METHODS: A comprehensive literature search of PubMed, Embase, Web of science, and Cochrane Library databases was conducted to screen the study literature based on inclusion and exclusion criteria to extract and analyze pre- and post-treatment pain score data, success rates (complete pain relief with no recurrence until the last follow-up), recurrence rates, secondary intervention rates, and complications to evaluate the efficacy and/or safety of MRgFUS for OO. RESULTS: A total of 113 studies published between 2012 and 2022were collected, resulting in a total sample size of 353 patients. The majority of the studies were prospective and had a follow-up period of 4 weeks or more, and overall, the quality of evidence ranged from low to high. Pain scores at 1 week and 1 month after the merger were 0.62 (9.5% CI:0.28-0.96) and 0.37 (9.5% CI:0.07-0.68), respectively. The success rate of the combination was 92.8% (95% CI: 89.8%-95.7%), the incidence of minor complications (thermal injury at the ablation site) was 0.85%, and no major complications were recorded in any of the included literature. CONCLUSION: MRgFUS is an effective procedure that is able to treat pain for patients with OO with satisfying efficacy and safety. PROSPERO: No.CRD42023415573.

Efficacy and safety of magnetic resonance-guided focused ultrasound for Parkinson's disease: a systematic review and meta-analysis.

Objective: Magnetic resonance imaging-guided focused ultrasound (MRgFUS) is a novel noninvasive treatment for drug-resistant Parkinson's disease (PD) related tremor. This study aims to evaluate MRgFUS's efficacy and safety in PD through a systematic review and meta-analysis, examining pre-and post-treatment MDS-UPDRSIII and/or CRST scores and associated adverse events. Materials and methods: We conducted an extensive literature search across PubMed, Embase, Web of Science, and Cochrane Library databases, screening studies based on set criteria and analyzing MDS-UPDRSIII, CRST, and adverse events pre- and post-MRgFUS treatment. Results: Out of 468 retrieved articles, 20 studies involving 258 patients, spanning 2014-2023, were included.17 studies indicated significant MDS-UPDRSIII score reductions post-MRgFUS treatment, while 3 showed significant CRST score declines. In the "on" medication state, pooled MDS-UPDRSIII scores at 1, 3, 6, and 12 months were 12.18 (95% CI: 5.83-18.52), 12.10 (95% CI: 8.22-15.97), 14.85 (95% CI: 9.28-20.41), and 20.65 (95% CI: 12.15-29.14) respectively. In the "off" state, scores were 11.45 (95% CI: -3.50-26.40), 14.71 (95% CI: 4.95-24.46), 21.52 (95% CI: 19.28-23.75), and 22.28 (95% CI: 15.26-29.30). Adverse events were typically mild and transient, with speech disturbances, ataxia, and sensory abnormalities being common post-operative neurological complications. Conclusion: MRgFUS offers an effective and relatively safe treatment option for patients with drug-resistant PD-related tremor. Systematic review registration: https://www.crd.york.ac.uk/prospero/, No. CRD42023428332.

DUF1005 Family Identification, Evolution Analysis in Plants, and Primary Root Elongation Regulation of CiDUF1005 From Caragana intermedia.

Proteins with a domain of unknown function (DUF) represent a number of gene families that encode functionally uncharacterized proteins in eukaryotes. In particular, members of the DUF1005 family in plants have a 411-amino-acid conserved domain, and this family has not been described previously. In this study, a total of 302 high-confidence DUF1005 family members were identified from 58 plant species, and none were found in the four algae that were selected. Thus, this result showed that DUF1005s might belong to a kind of plant-specific gene family, and this family has not been evolutionarily expanded. Phylogenetic analysis showed that the DUF1005 family genes could be classified into four subgroups in 58 plant species. The earliest group to emerge was Group I, including a total of 100 gene sequences, and this group was present in almost all selected species spanning from mosses to seed plants. Group II and Group III, with 69 and 74 members, respectively, belong to angiosperms. Finally, with 59 members, Group IV was the last batch of genes to emerge, and this group is unique to dicotyledons. Expression pattern analysis of the CiDUF1005, a member of the DUF1005 family from Caragana intermedia, showed that CiDUF1005 genes were differentially regulated under various treatments. Compared to the wild type, transgenic lines with heterologous CiDUF1005 expression in Arabidopsis thaliana had longer primary roots and more lateral roots. These results expanded our knowledge of the evolution of the DUF1005 family in plants and will contribute to elucidating biological functions of the DUF1005 family in the future.

Galactose-decorated pH-responsive nanogels for hepatoma-targeted delivery of oridonin.

Nanogels based on the polymers of galactosylated chitosan-graft-poly (N-isopropylacrylamide) (Gal-CS-g-PNIPAm) were used as carriers of oridonin (ORI) for tumor targeting. Three ORI-loaded nanogels with various degrees of galactose substitution were prepared, and their characteristics were evaluated. The release behavior of ORI from these nanogels was pH-dependent, and the release could be accelerated under mildly acidic conditions. The cytotoxicity of ORI-loaded nanogels was pH-sensitive. ORI-loaded nanogels exhibited a higher antitumor activity than drug-loaded nanogels without galactosylation, and the anticancer activity increased in relation to increases in the number of galactose moieties of the nanogels in HepG2 cells. In contrast, the cytotoxicity of ORI-loaded nanogels against MCF-7 cells decreased compared with that of drug-loaded nanogels without galactosylation. Results demonstrated that these nanogels could enhance the uptake of ORI into HepG2 cells via asialoglycoprotein receptor-mediated endocytosis. These galactose-decorated pH-responsive nanogels were well-suited for targeted drug delivery to liver cancer cells.

Involvement of protein S-nitrosylation in regulating beef apoptosis during postmortem aging.

This study was the first attempt to explore the effect of protein S-nitrosylation on the progress of apoptosis in postmortem beef semimembranosus muscle (SM). Five beef SM were incubated with S-nitrosoglutathione (GSNO, nitric oxide donor), control, or Nω-nitro-l-arginine methyl ester hydrochloride (l-NAME, nitric oxide synthase inhibitor). Results suggest that compared to the control, more chromatin condensation, nucleusfragmentation, apoptoticbody formation, and mitochondrialswelling were observed in the l-NAME group while these apoptosis-related morphological changes were retarded in the GSNO group. Notably, there were fewer apoptotic nuclei in the GSNO group and more apoptotic nuclei in the l-NAME group compared to the control (P < 0.05). Additionally, caspase-3 and -9 activities and caspase-3 activation were greatly decreased by GSNO treatment and increased by l-NAME treatment (P < 0.05). The morphological and biochemical results indicate that protein S-nitrosylation could play a negative regulatory role in beef apoptosis during postmortem aging.

Interplay of microRNAs to genetic, epigenetic, copy number variations of cervical cancer related genes.

This study was to analyses the miRNAs role in cervical cancer and possibilities of microRNA-based markers as diagnostic tools. Genome wide analysis was performed for CNV detection using PennCNV and QuantiSNP. The associated mRNA qRT-PCR detection was used to measure quantities of microRNA gene expression. More than 10 CNV regions has a significant relationship with cervical cancer risk for both CNV detection algorithms. A total of 34 CNVs was detected by QuantiSNP while it was 27 in case of PennCNV, among which 22 CNVs was found to be overlapping between these two algorithms. the mRNA was analyzed for its expression on 36 carvical tumor normal tissue pairs of four targets i.e., MAP3K3, RIPK2, DIRAS3 and GAS7. These infers that there was a significant downregulation of all the four genes cervical tumor. Our results showed that miR-182 can modulate the expression of FAM83H, DIRAS3, RIPK2 and MAP3K3 in cervical cancer. Therefore, indicated that miR-182 can acts through these signaling pathway in proliferation of cervical cancer cells. The expression of tumor modulator miRNAs can be controlled by miRNA replacement therapy. Several miRNAs have been used for this purpose. The modulation of various signaling pathway and proteins in cervical cancer cells by miR-182 needs further clarification.

Insight into the Effects of Sous Vide on Cathepsin B and L Activities, Protein Degradation and the Ultrastructure of Beef.

This study aimed to evaluate the effects of sous vide cooking (SV) on beef tenderness and its underlying potential mechanism. Beef semimembranosus (SM) were subjected to SV treatments at 45 °C, 55 °C and 65 °C for 4 h. Compared with control samples (CK, cooked at 75 °C until a core temperature of 72 °C was attained), SV treatment significantly promoted the release of cathepsin B and cathepsin L from lysosomes and decreased the shear force of beef SM (p < 0.05). In comparison with CK, samples treated with SV had more hydrolysis of myosin heavy chain and obtained higher myofibrillar fragmentation index, collagen solubility as well as longer sarcomere length (p < 0.05). The current study showed that the proteolysis of myofibrillar protein and collagen induced by cathepsin B and cathepsin L, and the limited longitudinal shrinkage together contributed to the improvement of beef tenderness upon SV.

Comparison of activity, expression and S-nitrosylation of glycolytic enzymes between pale, soft and exudative and red, firm and non-exudative pork during post-mortem aging.

The activity, expression and S-nitrosylation of glycogen phosphorylase (GP), phosphofructokinase (PFK) and pyruvate kinase (PK) was compared between pale, soft and exudative (PSE) and red, firm and non-exudative (RFN) pork. The nitric oxide synthase (NOS) activity of RFN pork was higher than PSE pork (P < 0.05). Glycogen and lactic acid content were significantly different between PSE and RFN samples at 1 h postmortem (P < 0.05). Compared to PSE pork, RFN pork had lower activities and higher S-nitrosylation levels of GP, PFK and PK (P < 0.05). Moreover, GP expression in RFN pork was lower (P < 0.05) while no significant differences of PFK and PK expression were observed between these two groups. These data suggest that protein S-nitrosylation can presumably regulate glycolysis by modulating glycolytic enzymes activities and then regulate the development of PSE pork.

Activity and mechanism of flavokawain A in inhibiting P-glycoprotein expression in paclitaxel resistance of lung cancer.

Lung cancer is one of the most common cancers, which is the leading cause of cancer-related death among various cancers worldwide. Flavokawain A (FKA), a chalcone found in the kava plant, exerts potent anticancer activity. However, the activity and mechanisms of FKA in inhibiting the viability of paclitaxel (PTX)-resistant lung cancer A549 (A549/T) have not been investigated. In the present study, the effect of FKA on the viability of A549/T and hepatotoxicity in normal liver epithelial cells was detected by Cell Counting Kit-8 assay. Flow cytometry, western blot analysis and Annexin V-FITC/PI apoptosis detection kit were used to assess cell apoptosis. The effect of FKA on permeability-glycoprotein (P-gp) expression was measured by reverse transcription-PCR and western blot analysis. The results indicated that FKA dose-dependently inhibited cell proliferation and induced cell apoptosis in PTX-resistant A549/T cells, with an IC50 value of ~21 µM, while the IC50 value of A549/T cells to PTX was 34.64 µM. FKA had no hepatic toxicity in liver epithelial cells. P-gp, which contributes to the chemoresistant phenotype, was not expressed in A549 cells but was remarkably enhanced in A549/T cells. FKA (30 µM) decreased P-gp protein expression at 24 h by 3-fold. Furthermore, FKA downregulated P-gp expression by blocking the PI3K/Akt pathway. These findings suggest FKA as a potential candidate for the treatment of PTX-resistant lung cancer.

Acetyl-11-keto-ß-boswellic acid triggers premature senescence via induction of DNA damage accompanied by impairment of DNA repair genes in hepatocellular carcinoma cells in vitro and in vivo.

Cellular senescence, a state of irreversible growth arrest, occurs in all somatic cells and causes the cells to exhaust replicative capacity. Recently, cellular senescence has been emerging as one of the principal mechanisms of tumor suppression, which can be induced by low doses of therapeutic drugs in cancer cells. Acetyl-11-keto-ß-boswellic acid (AKBA), an active ingredient isolated from the plant Boswellia serrata, has been identified to induce apoptosis in hepatocellular carcinoma (HCC) cells. In this study, we found that low concentrations of AKBA treatment triggered cell growth arrest at G0/G1 phase with features of premature cellular senescence phenotype in both HCC cell lines HepG2 and SMMC7721, as observed by enlarged and flattened morphology, significant increase in cells with senescence-associated ß-galactosidase staining, and decrease in cell proliferation and DNA synthesis. Furthermore, cellular senescence induced by AKBA occurred via activation of DNA damage response and impairment of DNA repair, as evidenced by strong induction of γH2AX and p53, and downregulated expressions of multiple DNA repair associated genes. Induction of p53 by AKBA caused a significant increase in p21CIP1 , which had a critical involvement in the induction of cellular senescence. Additionally, in vivo study demonstrated that induction of senescence contributed to the anticancer efficacy of AKBA. Therefore, our findings suggested that induction of premature senescence by AKBA through DNA damage response accompanied by impairment of DNA repair genes defines a novel mechanism contributing to its growth suppression in HCC cells.

Synergistic Combination of Sodium Aescinate-Stabilized, Polymer-Free, Twin-Like Nanoparticles to Reverse Paclitaxel Resistance.

BACKGROUND: The development of paclitaxel (PTX) resistance seriously restricts its clinical efficacy. An attractive option for combating resistance is inhibiting the expression of P-glycoprotein (P-gp) in tumor cells. We have reported that flavokawain A (FKA) inhibited P-gp protein expression in PTX-resistant A549 (A549/T) cells, indicating that FKA combined with PTX may reverse PTX resistance. However, due to the variable pharmacokinetics of FKA and PTX, the conventional cocktail combination in clinics may cause uncertainty of treatment efficacy in vivo. MATERIALS AND METHODS: To synergistically elevate the anti-cancer activity of PTX and FKA in vivo, the national medical products administration (NMPA) approved sodium aescinate (Aes) was utilized to stabilize hydrophobic PTX and FKA to form polymer-free twin like PTX-A nanoparticles (NPs) and FKA-A NPs. RESULTS: The resulting nanoparticles prepared simply by nanoprecipitation possessed similar particle size, good stability and ultrahigh drug loadings of up to 50%. With the aid of Aes, these two drugs accumulated in tumor tissue by passive targeting and were efficiently taken up by A549/T cells; this resulted in significant suppression of tumor growth in A549/T homograft mice at a low PTX dose (2.5 mg·kg-1). Synergistic effects and reversed PTX resistance were achieved by the combination of PTX-A NPs and FKA-A NPs by inhibiting P-gp expression in tumor cells. CONCLUSION: Using NMPA-approved Aes to prepare twin-like nanoparticles without introducing any new materials provides an efficient platform for combination chemotherapy and clinical translation.

Qualitative and quantitative analysis of Yifei Tongluo granules to identify main bioactive components using LC-DAD/MS and pharmacokinetic studies.

A standard fingerprint containing twelve common peaks was constructed from ten batches of Yifei Tongluo granules to evaluate batch-to-batch consistency by using HPLC-DAD. Additionally, the corresponding medicinal material attributes of these chemical constituents were analyzed according to the data acquired from the HPLC method and the identification was further carried out using the LC-MS/MS method. Comparing the retention time or accurate mass with previous studies or standards, the common components were tentatively identified in 50 min for ten batches of samples. At the same time, a reliable LC-MS/MS method was established to quantify marker substances simultaneously in 25 min, and the linear relationship of the standard curves was good in the experimental range. The validations of the method were successfully applied to the quality control and pharmacokinetic study. The results obtained from this study suggest that militarine was most abundant and the components in the granules caused pharmacokinetic herb-drug interactions in rats. This study provides a meaningful basis for evaluating the viability of Yifei Tongluo granules for clinical applications.

Expression of Pork Plectin during Postmortem Aging.

The current study investigated the distribution and degradation of pork plectin during postmortem aging. Longissimus thoracis (LT) muscles from 12 pig carcasses were vacuum-packaged and aged at 4 °C for 0 h, 6 h, 12 h, 1 day, 3 days, 7 days, and 13 days. Immunofluorescence analysis showed that pork plectin was distributed in a honeycomb-like pattern in the cross section and a regularly striated pattern in the longitudinal section. However, plectin was found preferentially expressed in fibers that were stained with high anti-fast-MyHC. Double immunostaining revealed the colocalization of plectin and desmin in the cytoplasm and beneath the sarcolemma. Western blot analysis showed that the amount of intact plectin was rapidly reduced during the early postmortem aging (P < 0.05) and almost disappeared at day 3. The degraded 240 kDa plectin accumulated fast and was further cleaved after 3 days of aging (P < 0.05). The plectin degradation could be significantly blocked by calpain inhibitor MDL-28170 rather than caspase-3 inhibitor Ac-DEVD-CHO (P < 0.05). Double immunostaining of µ-calpain and plectin showed a large amount of overlap at 0 h and 3 days of postmortem. Accordingly, these findings showed that plectin was preferentially expressed in fast muscle fiber and regularly distributed along with desmin at the strategic cellular sites. Plectin suffered a prominent and prompt degradation during postmortem aging, which might be attributed to µ-calpain.

Comparison of Activity, Expression, and S-Nitrosylation of Calcium Transfer Proteins between Pale, Soft, and Exudative and Red, Firm, and Non-exudative Pork during Post-Mortem Aging.

The research was performed to investigate the difference of activity, expression, and S-nitrosylation of calcium transfer proteins between pale, soft, and exudative (PSE) and red, firm, and non-exudative (RFN) pork. Seven PSE and seven RFN pork longissimus thoracis (LT) muscles were chosen according to pH and L* at 1 h post-mortem and identified by drip loss at 24 h. The nitric oxide synthase (NOS) activity and neuronal nitric oxide synthase (nNOS) expression showed a significant difference between two groups ( p < 0.05). PSE meat had a considerably higher sarcoplasmic calcium concentration compared to RFN meat at 1 h post-mortem aging ( p < 0.05). In PSE meat, the expression of ryanodine receptor 1 (RyR1) and sarcoplasmic reticulum calcium ATPase 1 (SERCA1) was lower than that in RFN meat, while the relative S-nitrosylation level of RyR1 and SERCA1 was higher ( p < 0.05). In addition, a lower activity of SERCA was detected in PSE meat compared to RFN meat ( p < 0.05). Those results indicate that S-nitrosylation of RyR1 and SERCA1 can putatively play a crucial part in regulating calcium homeostasis. A high level of RyR1 and SERCA1 S-nitrosylation can induce the imbalance of calcium in cytoplasm, leading to accelerated pH decline and the development of PSE meat.

Multifunctional mesoporous silica nanoparticles mediated co-delivery of paclitaxel and tetrandrine for overcoming multidrug resistance.

The objective of the study is to fabricate multifunctional mesoporous silica nanoparticles for achieving co-delivery of conventional antitumor drug paclitaxel (PTX) and the multidrug resistance reversal agent tetrandrine (TET) expecting to overcome multidrug resistance of MCF-7/ADR cells. The nanoparticles were facile to prepare by self-assemble in situ drug loading approach. Namely, PTX and TET were solubilized in the cetyltrimethylammonium bromide (CTAB) micelles and simultaneously silica resources hydrolyze and condense to form nanoparticles. The obtained nanoparticles, denoted as PTX/TET-CTAB@MSN, exhibited pH-responsive release property with more easily released in the weak acidic environment. Studies on cellular uptake of nanoparticles demonstrated TET could markedly increase intracellular accumulation of nanoparticles. Furthermore, the PTX/TET-CTAB@MSN suppressed tumor cells growth more efficiently than only delivery of PTX (PTX-CTAB@MSN) or the free PTX. Moreover, the nanoparticle loading drugs with a PTX/TET molar ratio of 4.4:1 completely reversed the resistance of MCF-7/ADR cells to PTX and the resistance reversion index was 72.3. Mechanism research showed that both TET and CTAB could arrest MCF-7/ADR cells at G1 phase; and besides PTX arrested cells at G2 phase. This nanocarrier might have important potential in clinical implications for co-delivery of multiple drugs to overcome MDR.

In vitro and in vivo evaluation of paclitaxel-loaded mesoporous silica nanoparticles with three pore sizes.

In the present study, mesoporous silica nanoparticles (MSNs) with three pore size were manufactured by the etch method. A typical chemotherapeutic agent, paclitaxel (PTX) was loaded into these MSNs. The in vitro drug release behavior, the in vitro anti-tumor activity, the morphological apoptosis cell changes, cell apoptosis rate and pharmacokinetics were extensively evaluated to clarify the biomedical roles of these MSNs in the application of drug delivery. The results showed that paclitaxel-loaded MSNs not only demonstrated effective drug loading but also exhibited pore-size-dependent drug release performance in vitro. In addition, MSNs exhibited pore-size-dependent anti-tumor activity against breast cancer MCF-7 cells. The apoptosis mechanism study demonstrated that the percentage of early and late apoptosis of all PTX-loaded MSNs treated MCF-7 cells were significantly higher than that of free PTX, and additionally the percentage of apoptosis for PTX-loaded MSNs increased as the pore size of carriers enlarged. The pharmacokinetics results showed that PTX-loaded MSNs with the largest pore size exhibited the pharmacokinetic property similar to the PTX solution and the other drug loaded MSNs displayed sustained release behavior. These results demonstrate that MSNs could be a very promising drug delivery system for pore-size controllable drug release and enhancing the anti-tumor activity.