CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

The molecular mechanism of chromatin assembly factor 1 unit A (CHAF1A) promoting the proliferation and growth of epithelial ovarian cancer (EOC) cells hasn't been reported at present. In this study, recombinant CHAF1A siRNA/overexpression plasmid (si-RNA1/pcDNA3.1-CHAF1A) was designed and constructed, and stable cell lines with knockdown or overexpression of CHAF1A were constructed. The changes of JAK2/STAT3 pathway were detected by Western blot. JAK2/STAT3 pathway was inhibited by Peficitinib, and then cell proliferation and growth ability were detected. Bioinformatics analysis suggested that CHAF1A was up-regulated in epithelial ovarian cancer. JAK2/STAT3 pathway phosphorylation was inhibited in si-RNA1 group, while it was increased in pcDNA3.1-CHAF1A group. After inhibiting JAK2/STAT3 pathway, the promoting effect of CHAF1A on epithelial ovarian cancer cell proliferation disappeared, meanwhile the inhibitory effect of CHAF1A on apoptosis enhanced. In conclusion, CHAF1A promotes the proliferation and growth of epithelial ovarian cancer cells by affecting the phosphorylation of JAK2/STAT3 signaling pathway.

In Situ Spatial Analysis of Metabolic Heterogeneity in Single Living Tumor Spheroids Using Nanocapillary-Based Electrospray Ionization Mass Spectroscopy.

Spatial metabolomic analysis of individual tumor spheroids can help investigate metabolic rearrangements in different cellular regions of a spheroid. In this work, a nanocapillary-based electrospray ionization mass spectroscopy (ESI-MS) method is established that could realize the spatial sampling of cellular components in different regions of a single living tumor spheroid and the subsequent MS analysis for a metabolic study. During the penetration of the nanocapillary into the spheroid for sampling, this "wound surface" at the outer layer of the spheroid takes only 0.1% of the whole area that maximally maintains the cellular activity inside the spheroid for the metabolic analysis. Using the ESI-MS analysis, different metabolic activities in the inner and outer (upper and lower) layers of a single spheroid are revealed, giving a full investigation of the metabolic heterogeneity inside one living tumor spheroid for the first time. In addition, the metabolic activities between the outer layer of the spheroid and two-dimensional (2D)-cultured cells show obvious differences, which suggests more frequent cell-cell and cell-extracellular environment interactions during the culture of the spheroid. This observation not only establishes a powerful tool for the in situ spatial analysis of the metabolic heterogeneity in single living tumor spheroids but also provides molecular information to elucidate the metabolic heterogeneity in this three-dimensional (3D)-cultured cell model.

The biological functions of europium-containing biomaterials: A systematic review.

The biological functions of rare-earth elements (REEs) have become a focus of intense research. Recent studies have demonstrated that ion doping or alloying of some REEs can optimize the properties of traditional biomaterials. Europium (Eu), which is an REE with low toxicity and good biocompatibility, has promising applications in biomedicine. This article systematically reviews the osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties of Eu-containing biomaterials, thereby paving the way for biomedical applications of Eu. Data collection for this review was completed in October 2022, and 30 relevant articles were finally included. Most articles indicated that doping of Eu ions or Eu-compound nanoparticles in biomaterials can improve their osteogenic, angiogenic, neuritogenic, antibacterial, and anti-tumor properties. The angiogenic, antibacterial, and potential neuritogenic effects of Eu(OH)3 nanoparticles have also been demonstrated.

Systematic in vitro and in vivo study on biodegradable binary Zn-0.2 at% Rare Earth alloys (Zn-RE: Sc, Y, La-Nd, Sm-Lu).

Biomedical implants and devices for tissue engineering in clinics, mainly made of polymers and stiff metallic materials, require possibly secondary surgery or life-long medicine. Biodegradable metals for biomedical implants and devices exhibit huge potential to improve the prognosis of patients. In this work, we developed a new type of biodegradable binary zinc (Zn) alloys with 16 rare earth elements (REEs) including Sc, Y, La to Nd, and Sm to Lu, respectively. The effects of REEs on the alloy microstructure, mechanical properties, corrosion behavior and in vitro and in vivo biocompatibility of Zn were systematically investigated using pure Zn as control. All Zn-RE alloys generally exhibited improved mechanical properties, and biocompatibilities compared to pure Zn, especially the tensile strength and ductility of Zn-RE alloys were dramatically enhanced. Among the Zn-RE alloys, different REEs presented enhancement effects at varied extent. Y, Ho and Lu were the three elements displaying greatest improvements in majority of alloys properties, while Eu, Gd and Dy exhibited least improvement. Furthermore, the Zn-RE alloys were comparable with other Zn alloys and also exhibited superior properties to Mg-RE alloys. The in vivo experiment using Zn-La, Zn-Ce, and Zn-Nd alloys as tibia bone implants in rabbit demonstrated the excellent tissue biocompatibility and much more obvious osseointegration than the pure Zn control group. This work presented the significant potential of the developed Zn-RE binary alloys as novel degradable metal for biomedical implants and devices.

Fungal polyketides from a rhizospheric soil-derived Penicillium sp. YUD17004 associated with Gastrodia elata.

Five unprecedented polyketide metabolites were isolated and characterized from a rhizospheric soil-derived Penicillium sp. YUD17004. Their diverse structures included two indanone-type polyketides penicillyketides A and B, a phthalide-like polyketides penicillyketide C, a symmetrical chromone dimer penicillyketide D, along with a pyrone derivative pyranlyketide, which were elucidated by spectroscopic data interpretation and quantum chemical electronic circular dichroism calculation. Notably, the structures of penicillyketides A and B feature a highly functionalized indanone ring nucleus, but differ from other indanone-containing polyketides by the alkyl substitution pattern. The structure of penicillyketide C comprises a furanone ring instead of the hydroxycyclopentenone ring characteristic for penicillyketides A and B, and represents an undescribed arrangement within C17 polyketides. Penicillyketide D represented the first example of a chromone homodimer with the bridge at C-2/2'. Penicillyketide B exhibited weak anti-inflammatory activity with an IC50 value of 32 ± 1.0 µM. Penicillyketide D displayed weak cytotoxicity against MCF-7 cell line with an IC50 value of 25 ± 0.9 µM.

The antifeedant and antifungal cryptic metabolites isolated from tobacco endophytes induced by host medium and coculture.

Four new cryptic metabolites including one fumagillol derivative (2), one cyclohexenone derivative (4), one 10-membered lactone (5), and one natural 4-epi-brefeldin C (8), along with seven known compounds were found from isogenesis endophytes Aspergillus fumigatus, Penicillium janthinellum, Nigrospora sp., and Stagonosporopsis sp. induced by host Nicotiana tabacum medium and co-culture. The structures were determined mainly by spectroscopic methods, including extensive 1D, 2D NMR, MS techniques, ECD calculation, and Mosher's method. Compound 2 possessed a novel 1, 3-dioxetane residue and cyclohexane-containing terpenoid skeleton. Compounds 2, 4-7 and 10 showed significant antifungal activities against the plant pathogen Nigrospora sp. with MICs of 1 µg/mL. 2, 4, 5-7, and 10 indicated antifungal activities against Penicillium janthinellum, Aspergillus fumigatus, Phomopsis sp., and Alternaria sp. with MICs ≤8 µg/mL. Compounds 2, 6-8, and 10 (50 µg/cm2) and microbial fermentation extracts (100 µg/cm2) showed antifeedant activities against silkworms with feeding deterrence indices of 21-100%.

NEUROD1 predicts better prognosis in pancreatic cancer revealed by a TILs-based prognostic signature.

It has been well-defined that tumor-infiltrating lymphocytes (TILs) play critical roles in pancreatic cancer (PaCa) progression. This research aimed to comprehensively explore the composition of TILs in PaCa and their potential clinical significance. A total of 178 samples from the TCGA and 63 samples from the GSE57495 dataset were enrolled in our study. ImmuCellAI was applied to calculate the infiltrating abundance of 24 immune cell types in PaCa and further survival analysis revealed the prognostic values of TILs in PaCa. Moreover, the Hallmark enticement analysis of differentially expressed genes (DEGs) between low- and high-risk groups was performed as well. Immunohistochemistry staining was used to evaluate NEUROD1 expression. As result, different kinds of TILs had distinct infiltrating features. In addition, Specific TILs subsets had notable prognostic values in PaCa. We further established a 6-TILs signature to assess the prognosis of PaCa patients. Kaplan-Meier and Cox regression analyses both suggested the significant prognostic value of the signature in PaCa. Based on the prognostic signature, we screened a great deal of potential prognostic biomarkers and successfully validated NEUROD1 as a novel prognostic biomarker in PaCa. Overall, the current study illuminated the immune cells infiltrating the landscape in PaCa and identified a TILs-dependent signature and NEUROD1 for prognostic prediction in PaCa patients.

Photocrosslinkable Col/PCL/Mg composite membrane providing spatiotemporal maintenance and positive osteogenetic effects during guided bone regeneration.

Guided bone regeneration membranes have been effectively applied in oral implantology to repair bone defects. However, typical resorbable membranes composed of collagen (Col) have insufficient mechanical properties and high degradation rate, while non-resorbable membranes need secondary surgery. Herein, we designed a photocrosslinkable collagen/polycaprolactone methacryloyl/magnesium (Col/PCLMA/Mg) composite membrane that provided spatiotemporal support effect after photocrosslinking. Magnesium particles were added to the PCLMA solution and Col/PCLMA and Col/PCLMA/Mg membranes were developed; Col membranes and PCL membranes were used as controls. After photocrosslinking, an interpenetrating polymer network was observed by scanning electron microscopy (SEM) in Col/PCL and Col/PCL/Mg membranes. The elastic modulus, swelling behavior, cytotoxicity, cell attachment, and cell proliferation of the membranes were evaluated. Degradation behavior in vivo and in vitro was monitored according to mass change and by SEM. The membranes were implanted into calvarial bone defects of rats for 8 weeks. The Col/PCL and Col/PCL/Mg membranes displayed much higher elastic modulus (p < 0.05), and a lower swelling rate (p < 0.05), than Col membranes, and there were no differences in cell biocompatibility among groups (p > 0.05). The Col/PCL and Col/PCL/Mg membranes had lower degradation rates than the Col membranes, both in vivo and in vitro (p < 0.05). The Col/PCL/Mg groups showed enhanced osteogenic capability compared with the Col groups at week 8 (p < 0.05). The Col/PCL/Mg composite membrane represents a new strategy to display space maintenance and enhance osteogenic potential, which meets clinical needs.

Mg/Al-LDH as a nano-adjuvant for pertussis vaccine: a evaluation compared with aluminum hydroxide adjuvant.

Background. Layered double hydroxide (LDH) has been demonstrated as a highly efficient antigen platform to induce effective and durable immune response. However, whether LDH nanoparticles could act as an adjuvant for pertussis vaccines is still unknown. Here we evaluated the potential of Mg/Al-LDH as a nano-adjuvant to improve immune response against pertussis and compared it with commercial aluminum hydroxide (AH) adjuvant.Method. The Mg/Al-LDH nanoparticles were synthesized by a hydrothermal reaction. The morphology, structure and size of Mg/Al-LDH were characterized by transmission electron microscope, x-ray diffraction and MALVERN particle analysis. The ovalbumin and Pertussis toxin (PTd) was adsorbed to Mg/Al-LDH. The immune response of antigen-LDH complex was evaluated in mice, compared with commercial adjuvant alum. Hematoxylin-eosin staining was used to evaluate the inflammatory response at injection site.Results. The synthetic Mg/Al-LDH nanoparticles showed a typical hexagonal lamellar structure. The average size of synthetic nanoparticles was 102.9 nm with PDI of 0.13 and zeta potential was 44.4 mV. Mg/Al-LDH nanoparticles effectively adsorbed protein antigen and mediated antigen uptake by DC cells. Animal experiments showed that Mg/Al-LDH gave enhancement in anti-pertussis toxin (PTd) humoral immune response, which was considerable to commercial AH adjuvant. Finally, Mg/Al-LDH produced a slighter inflammatory response than AH at injection site and this injury was quickly recovered.Conclusion. Our study demonstrated the potential of Mg/Al-LDH as an effective adjuvant for pertussis vaccine, which induced comparable antibody response and had a better safety compared with commercial AH adjuvant.

Redox/pH-Responsive Biodegradable Thiol-Hyaluronic Acid/Chitosan Charge-Reversal Nanocarriers for Triggered Drug Release.

Biodegradable nanoparticles and micelles are promising nanosystems for the targeted delivery of potent anticancer drugs. By using specialized polymers as nanocarriers, targeted drug delivery and release can be developed. We developed thiol-hyaluronic acid (HA-SH)/chitosan (CS) nanoparticles with redox/pH dual-responsiveness via electrostatic self-assembly followed by spontaneous chemical cross-linking. The nanoparticle surface charges were reversible through different HA-SH and CS mass ratios. Doxorubicin (DOX) was used as a model drug. Dual cross-linked nanoparticles with diameters of approximately 300 nm exhibited superior stability under physiological conditions compared with nanoparticles without disulfide cross-linking. DOX was loaded more efficiently into negative nanoparticles (45.7 wt%) than positive nanoparticles (14.2 wt%). Drug release from negative nanoparticles (ζ potential of approximately -20) was higher (87.8 wt%) at pH 4.5 and in the presence of 10 mM glutathione. Positive nanoparticles (ζ potential of approximately +20) showed the same trend, but the release rate was slower than that of negative nanoparticles. DOX-loaded HA-SH/CS particles were taken up by human breast cancer cells (SKBR3), and the loaded drug was released, exhibiting potential antitumor efficacy. The HA-SH/CS nanoparticles in this study were stable under physiological conditions and are promising candidates for the targeted delivery and release of anticancer drugs.

Discovery of a covalent inhibitor of heat shock protein 90 with antitumor activity that blocks the co-chaperone binding via C-terminal modification.

Heat shock protein (Hsp90), a critical molecular chaperone that regulates the maturation of a large number of oncogenic client proteins, plays an essential role in the growth of neoplastic cells. Herein, DDO-6600 is identified to covalent modification of Cys598 on Hsp90 from in silico study and is verified by a series of biological assays. We demonstrated that DDO-6600 covalently bound to Cys598 on the Hsp90 C terminus and exhibited antiproliferative activities against multiple tumor cells without inhibiting ATPase activity. Further studies showed that DDO-6600 disrupted the interaction between Hsp90 and Cdc37, which induced the degradation of kinase client proteins in multiple tumor cell lines, promoted apoptosis, and inhibited cell motility. Our findings offer mechanic insights into the covalent modification of Hsp90 and provide an alternative strategy for the development of Hsp90 covalent regulators or chemical probes to explore the therapeutical potential of Hsp90.

miR-29a in Exosomes from Bone Marrow Mesenchymal Stem Cells Inhibit Fibrosis during Endometrial Repair of Intrauterine Adhesion.

BACKGROUND AND OBJECTIVES: Bone marrow mesenchymal stem cells (BMSCs) is an ideal source of stem cells in the treatment of intrauterine adhesion. Exosomes are a type of membrane vesicle and the diameter is 30∼100 nm. Exosomes can take their contents into the target cells, releasing and exerting their functions. In this study, we intend to study the role of human BMSC-derived exosomes (BMSC-Exo) in promoting endometrial damage repair in the treatment of IUA. METHODS: We used the magnetic bead affinity method to extract BMSC-Exo and analyzed its biological character. Then we co-cultured the BMSCs-Exo with endometrial cells to detect its effect. We injected BMSCs-Exo into the IUA mouse model. We over-expressed miR-29a in BMSCs-Exo by transient transfection, then used RT-PCR to analyze the expression of the related genes. RESULTS: BMSCs-Exo expressed exosome-specific proteins CD9, CD63, and CD81. BMSCs-Exo could bring the contents into the target cells. BMSCs-Exo can promote endometrial repair in vitro or in vivo. BMSCs-Exo overexpressing miR-29a can reduce αSMA, Collagen I, SMAD2, and SMAD3. CONCLUSIONS: In this study, we successfully isolated BMSCs-Exo and proved its character and biological activity. BMSCs-Exo can promote cell proliferation and cell migration in vitro and can repair damaged endometrium in the IUA model. The presence of miR-29a in BMSCs-Exo may be an important factor in its resistance to fibrosis during endometrial repair of IUA. This study provides new ideas for the treatment of patients with IUA and has important clinical research significance.

BRCA1 Is a Novel Prognostic Indicator and Associates with Immune Cell Infiltration in Hepatocellular Carcinoma.

The breast cancer gene 1 (BRCA1) is a tumor suppressor, and mutations or epigenetic inactivation will increase the risk of breast cancer oncogenesis. The current research aimed to explore the relationship between BRCA1 expression, prognosis, and tumor immunity in hepatocellular carcinoma (HCC). In this study, BRCA1 expression was analyzed via multiple online databases and its association with clinical characteristics, prognosis and genetic alterations was identified using the original The Cancer Genome Atlas-liver hepatocellular carcinoma cohorts. DNA methylation sites and their prognostic values were analyzed using MethSurv. The correlations between BRCA1 and immune infiltration were investigated via Tumor Immune Estimation Resource. As results, BRCA1 was significantly upregulated in tumor tissues in multiple HCC cohorts. Besides, high BRCA1 expression was correlated with race, advanced T stage, clinical stage, poor tumor grade, MSI status, and worse prognosis. Notably, BRCA1 expression was positively correlated with infiltration levels of B cells, CD4+ T cells, CD8+ T cells, neutrophils, macrophages, and dendritic cells. The current findings imply that BRCA1 is associated with prognosis and immune infiltration, laying foundations for in-depth research on the role of BRCA1 in HCC.

Systematic summarization of the expression profiles and prognostic roles of the dishevelled gene family in hepatocellular carcinoma.

BACKGROUND: Dishevelled (DVL) family members are crucial to Wnt-induced signaling transduction, and their expression is highly correlated with the progression of multiple malignant cancers. However, the expression profiles and exact prognostic values of DVLs in hepatocellular carcinoma (HCC) have not been explored until now. METHODS: The expression of DVL isoforms was assessed using the Oncomine, HCCDB and UALCAN databases. The prognostic roles of DVLs were further evaluated using the GEPIA database. The relationship between the expression of DVLs and immune infiltration of HCC was investigated using the Timer and ImmuCellAI tools. Furthermore, protein-protein interaction (PPI) networks were built and enrichment analyses were conducted. RESULTS: We found that the expression levels of DVL2 (OMIM accession number: 602151) and DVL3 (OMIM accession number: 601368) were upregulated in HCC tissues as revealed by the Oncomine and HCCDB databases. Additionally, the expression of DVLs tended to be associated with advanced clinical features in the UALCAN database. Prognostic analysis revealed that the expression levels of DVL1 (OMIM accession number: 601365) and DVL3 were remarkably associated with a poor prognosis in HCC patients. The results also revealed that the DVL expression level was correlated with the infiltration levels of multiple immune cells. By constructing the PPI network and enrichment analyses, the DVL1-3 gene was identified to interact with 20 key genes and participate in several pathways. CONCLUSION: In summary, DVL2 and DVL3 are highly expressed in HCC, and DVL1 and DVL3 are related to a poor prognosis, which might be used as candidate targets for targeted therapy and reliable prognostic biomarkers in HCC.

LAMA2 regulates the fate commitment of mesenchymal stem cells via hedgehog signaling.

BACKGROUND: Bone defects are a common clinical condition that has gained an increasing amount of attention in recent years. Causes of bone defect include tumors, inflammation, and fractures. Bone tissue engineering is a novel treatment of bone defect, and human mesenchymal stem cells (hMSCs) are the ideal seed cells for bone tissue engineering due to their multi-lineage differentiation potential and immunogenicity. The laminin α2 (LAMA2) gene encodes the α2 subunit of laminins. Mutations in this gene have been reported to cause muscular dystrophy, but thus far no studies have elucidated the role of LAMA2 in the fate choices of MSCs. Here, we aimed to investigate the critical role of LAMA2 in the osteogenesis and adipogenesis of mesenchymal stem cells (MSCs). METHODS: We investigated LAMA2 function in osteogenic and adipogenic differentiation of MSCs in vitro and in vivo through loss- and gain-of-function experiments. In addition, molecular mechanism was clarified by Western blot and siRNA. RESULTS: Our results demonstrated that LAMA2 was a critical regulator for fate commitment of MSCs. Both in vitro and in vivo studies indicate that LAMA2 inhibits osteogenesis and promotes adipogenesis. Mechanistically, we found that LAMA2 regulated osteogenesis and adipogenesis of MSCs by modulating the hedgehog signaling pathway. CONCLUSIONS: The present work confirms that LAMA2 is a new molecular target for MSC-based bone regeneration.

Fabrication and Application of a 3D-Printed Poly-ε-Caprolactone Cage Scaffold for Bone Tissue Engineering.

Poly-ε-caprolactone (PCL) is a promising synthetic material in bone tissue engineering (BTE). Particularly, the introduction of rapid prototyping (RP) represents the possibility of manufacturing PCL scaffolds with customized appearances and structures. Bio-Oss is a natural bone mineral matrix with significant osteogenic effects; however, it has limitations in being constructed and maintained into specific shapes and sites. In this study, we used RP and fabricated a hollow-structured cage-shaped PCL scaffold loaded with Bio-Oss to form a hybrid scaffold for BTE. Moreover, we adopted NaOH surface treatment to improve PCL hydrophilicity and enhance cell adhesion. The results showed that the NaOH-treated hybrid scaffold could enhance the osteogenesis of human bone marrow-derived mesenchymal stem cells (hBMMSCs) both in vitro and in vivo. Altogether, we reveal a novel hybrid scaffold that not only possesses osteoinductive function to promote bone formation but can also be fabricated into specific forms. This scaffold design may have great application potential in bone tissue engineering.

A pure zinc membrane with degradability and osteogenesis promotion for guided bone regeneration: In vitro and in vivo studies.

Selection of an appropriate membrane material for guided bone regeneration (GBR) is still ongoing among resorbable and nonresorbable membranes with different characteristics. The major problem with nonresorbable membranes is the inevitable secondary surgery, while resorbable polymer membranes have limitations in providing sufficient mechanical support during the bone repair period due to premature loss of mechanical strength. Pure magnesium foil has been evaluated to explore its feasibility as a resorbable GBR membrane. It exhibited better mechanical properties, whereas poor formability and fast degradation rate were noted. In light of this, pure zinc membrane was developed as a pilot research in this paper. We designed three types of pure zinc membranes: pure Zn without pores, pure Zn with 300 µm diameter and 1000 µm diameter pores, and pure titanium without pores as a control. The mechanical property, in vitro immersion tests, and MC3T3-E1 cell viability assays were tested. Moreover, in vivo behaviors of three type zinc membranes were evaluated by using a rat calvarial critical-sized bone defect model. The experimental results indicated that pure Zn membrane with 300 µm pores showed the most favorable osteogenic capability, comparable to that of titanium membrane without pores. Therefore, considering appropriate degradation rate, adequate mechanical maintenance, and profitable osteogenic capacity, metallic pure zinc is believed to be a promising candidate for barrier membranes in GBR therapy for bone regeneration, and its mechanical property can be enhanced with further alloying. STATEMENT OF SIGNIFICANCE: Metallic element zinc plays a pivotal role in the growth and mineralization of bone tissues. As a pilot research, three type of guided bone regeneration (GBR) membranes were developed in the present work: pure Zn without pores, pure Zn with 300 µm-diameter and 1000 µm-diameter pores respectively. The mechanical property, in vitro immersion tests and MC3T3-E1 cell viability assays were tested, with pure titanium without pores as a control, thereafter the in vivo performance were evaluated by using a rat calvarial critical-sized bone defect model. It indicated that pure Zn membrane with 300 µm pores showed the most favorable osteogenic capability, comparable to that of titanium membrane control, and is believed to be a promising material candidate as barrier membrane in GBR therapy for bone regeneration.

NY-ESO-1 expression in solid tumors predicts prognosis: A systematic review and meta-analysis.

BACKGROUND: New York esophageal squamous cell carcinoma 1 (NY-ESO-1) is a member of the cancer testis antigen family. NY-ESO-1 has documented potential as an effective target for cancer immunotherapy. The prognostic value of NY-ESO-1 expression in solid tumors, however, remains controversial because of inconclusive data. METHODS: For this analysis, the Medline, Embase, and Cochrane Library databases were searched up to February 2018 for studies investigating NY-ESO-1 expression in solid tumors and overall survival (OS), progression-free survival (PFS), or disease-free survival (DFS). Hazard ratios (HRs) with 95% confidence intervals (CIs) were extracted from each study. Pooled HRs and CIs were calculated using the Mantel-Haenszel fixed effects or random effects model. RESULTS: A total of 23 studies were included in the analysis. The combined HR (95% CI) estimates for OS, PFS, and DFS were 1.41 (95% CI: 1.24-1.61; I = 0%), 1.62 (95% CI: 1.42-1.84; I = 17%), and 0.95 (95% CI: 0.56-1.59; I = 57%), respectively. CONCLUSIONS: NY-ESO-1 expression in solid tumors is associated with worse OS and PFS. Studies are still needed to provide more evidence.

Low concentration flufenamic acid enhances osteogenic differentiation of mesenchymal stem cells and suppresses bone loss by inhibition of the NF-κB signaling pathway.

BACKGROUND: As the representative of fenamic acids, an important group of NSAIDs, flufenamic acid (FFA) has been used for anti-inflammation and analgesia in the clinic. Recently, researches have focused on the role of some members of NSAIDs in promoting osteogenesis. However, little attention has been paid to the subgroup of fenamic acids, and it remains unclear whether FFA and other fenamic acids could regulate mesenchymal stem cells' (MSCs) lineage commitment and bone regeneration. METHODS: Here we treated two kinds of human MSCs with FFA at different concentrations in vitro and examined the effect of FFA on osteogenic differentiation of human MSCs. This was followed by heterotopic bone formation assay in nude mice. In addition, ovariectomized and aged mice were used as osteoporotic models to test the effect of FFA on osteoporosis. Besides, activators and inhibitor of nuclear factor-κB (NF-κB) signaling pathway and western blot were used to clarify the mechanism of the promoting effect of low concentration FFA on osteogenesis. RESULTS: Our results indicated that low concentrations of FFA could significantly enhance osteogenic differentiation of human MSCs in vitro, as well as in vivo. In addition, FFA treatment suppressed bone loss in ovariectomized and aged mice. Mechanistically, FFA at low concentrations promoted osteogenesis differentiation of human MSCs by inhibition of the NF-κB signaling pathway. CONCLUSIONS: Collectively, our study suggested that low concentration FFA could be used in bone tissue engineering or osteoporosis by promoting osteogenic differentiation of human MSCs.

High-dose fulvestrant as third-line endocrine therapy for breast cancer metastasis to the left kidney: A case report and literature review.

RATIONALE: Endocrine therapy plays an important role in the treatment of patients with hormone receptor-positive breast cancer. Renal metastasis of breast cancer is rare in clinical practice. PATIENT CONCERNS: We present here a 54-year-old woman with breast cancer after first line chemotherapy and second line endocrinotherapy (i.e., toremifene & exemestane) failure. DIAGNOSES: The patient was rarely diagnosed breast cancer metastasis to the kidney and a positive hormone status (ER and PR) but was negative for human epidermal factor receptor 2 (HER2). INTERVENTIONS: The patient was treated with a high dose of fulvestrant (SERD; 500 mg) by intramuscular injection once per month. OUTCOMES: The patient's condition significantly improved as measured by a decrease in the renal and pulmonary masses; symptoms including dry cough and blood phlegm also improved. LESSONS: Endocrinotherapy with high-dose fulvestrant may provide benefits for patients with HR+/HER2- advanced breast cancer with renal metastasis after SERMs failure.