Role of Caveolae family-related proteins in the development of breast cancer.

Breast cancer has become the most significant malignant tumor threatening women's lives. Caveolae are concave pits formed by invagination of the plasma membrane that participate in many biological functions of the cell membrane, such as endocytosis, cell membrane assembly, and signal transduction. In recent years, Caveolae family-related proteins have been found to be closely related to the occurrence and development of breast cancer. The proteins associated with the Caveolae family-related include Caveolin (Cav) and Cavins. The Cav proteins include Cav-1, Cav-2 and Cav-3, among which Cav-1 has attracted the most attention as a tumor suppressor and promoting factor affecting the proliferation, apoptosis, migration, invasion and metastasis of breast cancer cells. Cav-2 also has dual functions of inhibiting and promoting cancer and can be expressed in combination with Cav-1 or play a regulatory role alone. Cav-3 has been less studied in breast cancer, and the loss of its expression can form an antitumor microenvironment. Cavins include Cavin-1, Cavin-2, Cavin-3 and Cavin-4. Cavin-1 inhibits Cav-1-induced cell membrane tubule formation, and its specific role in breast cancer remains controversial. Cavin-2 acts as a breast cancer suppressor, inhibiting breast cancer progression by blocking the transforming growth factor (TGF-ß) signaling pathway. Cavin-3 plays an anticancer role in breast cancer, but its specific mechanism of action is still unclear. The relationship between Cavin-4 and breast cancer is unclear. In this paper, the role of Caveolae family-related proteins in the occurrence and development of breast cancer and their related mechanisms are discussed in detail to provide evidence supporting the further study of Caveolae family-related proteins as potential targets for the diagnosis and treatment of breast cancer.

The relationship between the Hippo signaling pathway and bone metastasis of breast cancer.

Bone is the most common site of metastasis from breast cancer, which is the most prevalent cancer affecting women globally. Bone metastasis from breast cancer severely affects the quality of life of patients and increases mortality. The molecular mechanisms of metastasis, colonization, and proliferation of breast cancer cells in bone are complex and involve the interaction between breast cancer cells and the bone microenvironment. However, the precise mechanism is not clear at present. In recent years, the Hippo signaling pathway has attracted much attention due to its important role in regulating the expression of major effector molecules during tumor development. In particular, studies have found that the mutation and aberrant expression of the core components of the Hippo signaling pathway affect breast cancer cell migration and invasion, indicating that this pathway plays a role in bone metastasis, although the molecular mechanism of this pathway in breast cancer metastasis has not been fully elucidated. In this review, we discuss the function of the Hippo signaling pathway, introducing its role in breast cancer metastasis, especially bone metastasis of breast cancer, so as to lay a solid theoretical foundation for further research and for the development of effective targeted therapeutic agents.

Study on repair of abdominal wall defect rats with hernia mesh coated with chitosan-based photosensitive hydrogel.

Herein, hydroxypropyl chitosan azide (AZ-HPCTS) was synthesized and prepared as a hydrogel coating applied to a polypropylene mesh (PPM) through UV irradiation. This study confirmed the hypothesis that hydrogels with porous three-dimensional network structures exhibited excellent biocompatibility and biodegradability and adhered well to PPM. During the 180-day follow-up period, the AZ-HPCTS-coated PPM (AH-PPM) promoted wound healing by promoting the secretion of transforming growth factor-beta1 (TGF-beta1) in the acute reaction stage, which was reduced to a lower level at 30 d. The PPM exhibited a lower fibrin lysozyme activity based on the expression of tissue plasminogen activator (tPA) compared with that of AH-PPM (P < 0.05). The intraperitoneal adhesion score of AH-PPM decreased to 2.4 at 180 d in contrast with PPM (P < 0.01), which remained at a high level throughout the study. In conclusion, the AZ-HPCTS hydrogel is a potential coating for hernia patches that deserves further study in the biomaterial field.

Multifunctional effects of wound dressing based on chitosan-coordinated argentum with resistant bacterial penetration.

Third-degree scald, causing serious tissue destruction with continuous pain, easily leads to microbial infections and delayed wound healing. Therefore, a multifunctional treatment is attractive for seriously damaged tissue. Herein, carboxymethyl chitosan-coordinated argentum (Ag-CMC) was synthesized via a complexation method, and then the Ag+ release, antibacterial activity, biocompatibility, pain relief and wound healing properties of Ag-CMC were investigated in vitro and in vivo. The results revealed that Ag+ had interacted with carboxymethyl chitosan, containing approximately 1.2% of silver. The Ag-CMC (50-200 µg/mL) with Ag+ sustained release exhibited significant antibacterial activity against Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, Candida albicans, drug-resistant E. coli, PA, MRSA and good biocompatibility with L929 cells. Furthermore, antibacterial and wound healing experiments demonstrated that Ag-CMC achieved an effective contraction rate of 90% after 28 days by accelerating re-epithelialization, regulating inflammation response, relieving pain and infections. Therefore, Ag-CMC is a safe multifunctional treatment for wound healing and infections.

Functional thermosensitive hydrogels based on chitin as RIN-m5F cell carrier for the treatment of diabetes.

Herein, the thermosensitive hydroxypropyl chitin (HPCT) hydrogel was prepared and the chemical structures, microstructures, rheological properties and degradation in vitro were investigated. The HPCT hydrogel possessed satisfactory biocompatibility in mouse fibroblast cells and Sprague Dawley rats. On the other hand, N-acetylglucosamine (NAG) and carboxymethyl chitosan (CMCS) provided favorable capacity for promoting cell proliferation, delaying cell apoptosis, and facilitating the insulin secretion of rat pancreatic beta cells (RIN-m5F) in three-dimensional culture. Most importantly, the effects of HPCT/NAG and HPCT/CMCS thermosensitive hydrogels as RIN-m5F cells carriers were evaluated via injection into different areas of diabetic rats. Our results demonstrated that HPCT/NAG and HPCT/CMCS hydrogels loaded RIN-m5F cells could keep cells survival, maintain insulin secretion and reduce blood glucose for one week. Overall, the functional thermosensitive hydrogels based on HPCT were effective cell carriers for RIN-m5F cells and might provide novel strategy for the treatment of diabetes via cell engineering.

Injectable self-crosslinking hydrogels based on hyaluronic acid as vitreous substitutes.

After vitrectomy, the ideal vitreous substitute should be implanted to maintain the normal function of the eye. However, the existing materials (such as silicone oil, air, perfluorocarbons, etc.) still have some shortcomings and cannot fully meet the clinical needs. In this study, thiolated hyaluronic acid (SH-HA) was prepared based on hyaluronic acid. The SH-HA hydrogel was formed by a simple transformation of the sulfhydryl group to the disulfide bond, which had high transparency, controllable swelling property, suitable mechanical strength, excellent biocompatibility and similar physical and chemical properties to natural vitreous. SH-HA hydrogel was filled into the eyes of experimental rabbits to replace their own vitreous after vitrectomy. During the 90 days follow-up period, SH-HA hydrogel showed excellent intraocular compatibility, maintained normal intraocular pressure (IOP), and no cataract, endophthalmitis, retinal detachment and other complications were observed. In general, SH-HA hydrogel has great potential as a vitreous substitute.

Preparation, biocompatibility, and wound healing effects of O-carboxymethyl chitosan nonwoven fabrics in partial-thickness burn model.

This study was aimed at preparing O-carboxymethyl chitosan (CM-CTS) fabrics, and examining the wound healing effects on partial-thickness burn. The functional polysaccharides were produced from chitosan needle-punched nonwovens reacted with chloroacetic acid. Then the biocompatibility and biological functions were evaluated through fibroblast L-929 and SD rats. CM-CTS fabrics were obtained with elongation at break more than 42%, tensile strength reaching 0.65 N/mm2, and water vapor transmission rate about 2600 g/m2∙24 h. Moreover, CM-CTS fabrics could effectively promote the mouse L-929 migration in vitro. CM-CTS fabrics yielded satisfactory results in angiogenesis, collagen deposition, interleukin-6 content, transforming growth factor level and healing rate, which were superior to the positive control and model groups after rats suffering with partial-thickness burn. In conclusion, CM-CTS fabrics possessed proper mechanical properties, air permeability, favorable biocompatibility, acceleration on fibroblasts migration and healing capacity for partial-thickness burn injury, and owned good potential as high-quality wound dressing.

Preparation, Characterization, and Biological Evaluation of Transparent Thin Carboxymethyl-Chitosan/Oxidized Carboxymethyl Cellulose Films as New Wound Dressings.

Full thickness burns in which the damage penetrates deep into the skin layers and reaches underneath the muscle, compel the need for more effective cure. Herein, cross-linked carboxymethyl-chitosan (CM-chitosan) films, prepared by Schiff base association with oxidized carboxymethyl cellulose (OCMC), are investigated regarding the wound healing capacity on full thickness burn injuries in vivo. Transparent thin CM-chitosan/OCMC films are obtained with tensile strength reaching 6.11 MPa, elongation at break above 27%, and water absorption more than 800%, which operates in favor of absorbing excess exudate and monitoring the wound status. Furthermore, the nonadherent CM-chitosan/OCMC films, with satisfactory biodegradability, cell, and tissue compatibility, are readily used to the wound sites and easily removed following therapy on scalded tissue so as to alleviate the suffering from burn. The films efficiently promote epithelial and dermal regeneration compared to the control, achieving 75.9% and 94.4% wound closure, respectively, after 14 and 27 days. More importantly, CM-chitosan/OCMC films accelerate wound healing with natural mechanisms which include controlling inflammatory response, reducing apoptosis, promoting fibroblast cell proliferation, and collagen formation. In conclusion, the CM-chitosan/OCMC films elevate the repair ratio of burn injuries and have great potential for facilitating the healing process on full-thickness exuding wounds.

A self-healing and injectable hydrogel based on water-soluble chitosan and hyaluronic acid for vitreous substitute.

Vitreous, an essential dioptric medium for the human eyes, must be filled with artificial materials once damaged. Carboxymethyl chitosan (CMCTS) is one of the most important water-soluble chitosan derivatives with improved biocompatibility and biodegradability. In this study, oxidized hyaluronic acid (OHA) was prepared as crosslinking reagent. CMCTS and OHA were used to develop a biocompatible, self-repairing and in-situ injectable hydrogel for vitreous substitutes. Results showed the hydrogel with controllable swelling properties, high transparency, acceptable cytocompatibility on mouse fibroblast L929 and histocompatibility in vivo. Furthermore, hydrogel was injected in-situ into the vitreous cavity after vitrectomy on New Zealand Rabbits, no significant and persistent adverse effects were observed during the 90-day follow-up period. In addition, the hydrogel maintained intraocular pressure of the operated eyes and the inherent position of the retina. Collectively, this injectable, biodegradable, nontoxic hydrogel possessed enormous potential to become a vitreous substitute material.

Iron deficiency in late pregnancy and its associations with birth outcomes in Chinese pregnant women: a retrospective cohort study.

BACKGROUND: Several biomarkers are used to measure iron deficiency (ID) during pregnancy, but the prevalence of ID and its association with adverse birth outcomes shows inconsistent results. The aim of this study was to examine the prevalence of ID in third trimester using multiple indicators of iron status and the relationship with birth outcomes in Chinese population. METHODS: We conducted a retrospective observational cohort study of 11,581 pregnant women between 2016 and 2017 in Changzhou City, Jiangsu Province, China. We obtained the data (maternal characteristics and birth outcomes) and the concentrations of ID biomarkers from our hospitalization information system and laboratory information system, respectively. Using serum ferritin (SF), serum transferrin (ST) and their ratio as criteria of ID, we investigated associations between birth outcomes and late pregnancy ID. RESULTS: The prevalence of ID in our study was 51.82% as defined by low SF (< 12 µg/L), 54.43% as defined by high ST (> 4 g/L) and 53.90% as defined by high ratio of ST/SF (Log 10 transform > 5.52). Maternal ST/SF ratio was associated with higher mean birth weight (97.04 g; 95% CI, 74.28, 119.81 for the highest vs. lowest quartile). Third trimester maternal ID, defined by ST/SF ratio, was associated with lower risks of preterm birth (PTB), low birth weight (LBW) and small for gestational age (SGA) infants, higher risks of macrosomia and large for gestational age (LGA) babies (for PTB: OR = 0.53, 95% CI, 0.36-0.77; for LBW: OR = 0.44, 95% CI, 0.31-0.62; for SGA: OR = 0.69, 95% CI, 0.57-0.83; for macrosomia: OR = 1.39, 95% CI, 1.13-1.70; for LGA: OR = 1.20, 95% CI, 1.04-1.39). CONCLUSIONS: ID in the third-trimester of pregnancy are frequent in Chinese women. Our findings suggest that the ratio of ST/SF measured in late pregnancy could be useful as a significant predictor of unfavorable birth outcomes.

Evaluation of grain yield based on digital images of rice canopy.

BACKGROUND: Rice canopy changes are associated with changes in the red light (R), green light (G), and blue light (B) value parameters of digital images. To rapidly diagnose the responses of rice to nitrogen (N) fertilizer application and planting density, a simple model based on digital images was developed for predicting and evaluating rice yield. RESULTS: N application rate and planting density had significant effects on rice yield. Rice yield first increased and then decreased with increasing of N rates, while the rice yield always increased significantly with increasing planting density. The normalized redness intensity (NRI), normalized greenness intensity (NGI), and normalized blueness intensity (NBI) values of the rice canopy varied among stages; however, they were primarily affected by N fertilizer rates, while planting density had no significant effects. Furthermore, the significant relationships of grain yield with NRI and NBI at the late filling stage could be fitted by quadratic equations, but there was no significant relationship observed between grain yield and NGI across all stages. In addition, a field validation experiment showed that the predicted yield based on the fitted quadratic equations was consistent with the measured yield. CONCLUSION: The NRI, NGI, and NBI values of rice canopy were mainly affected by N fertilizer rates, while the planting density had no significant effect. The significant relationships between grain yield with NRI and NBI at the late filling stage could be fitted by quadratic equations. Therefore, the canopy NRI and NBI at the late filling stage as measured by digital photography could be used to predict grain yield in southern China.

Therapeutic Antidepressant Potential of NONHSAG045500 in Regulating Serotonin Transporter in Major Depressive Disorder.

BACKGROUND Major depressive disorder (MDD) is a chronic, life-threatening, highly disabling disease. Standardized treatment with fewer adverse effects, quick onset, and long-term maintenance of the effects of brief treatment for MDD is always being pursued. Long non-coding RNAs (lncRNAs) are highly expressed in the central nervous system and are involved in the occurrence and development of neurodegenerative and psychiatric diseases. This study aimed to investigate whether the overexpression and interference of 3 differentially down-regulated lncRNAs (NONHSAT142707, NONHSAG045500, and ENST00000517573) in MDD can affect the expression of central neurotransmitter serotonin (5-hydroxytryptamine) transporter (SERT) in vitro. MATERIAL AND METHODS First, we synthesized and validated the effect of 3 lncRNA plasmids and small interfering RNAs (siRNAs); next, we transfected the plasmids and siRNAs that caused significant overexpression or interference in SK-N-SH cells, and tested the expression of SERT by qRT-PCR. RESULTS The results showed that 3 lncRNA plasmids and siRNAs2 caused overexpression and interference, respectively. Only the overexpression of NONHSAG045500 could significantly inhibit the expression of SERT; interference with NONHSAG045500 could significantly strengthen the expression of SERT. CONCLUSIONS This study indicated that the expression of SERT could be regulated by up-regulating or down-regulating NONHSAG045500 expression and suggested that NONHSAG045500 could potentially be established as a new therapeutic target of MDD. Future work may be needed to definitively determine the correlation between NONHSAG045500 and SERT in vivo.

Cross-talk between freezing response and signaling for regulatory transcriptions of MIR475b and its targets by miR475b promoter in Populus suaveolens.

MicroRNAs (miRNAs) are small, non-coding RNAs that play important roles in post-transcriptional regulation of their target genes, yet the transcriptional regulation of plant miRNAs by promoter is poorly understood. Here, we firstly clone pri-miR475b cDNA and its native promoter from P. suaveolens, and characterize Psu-MIR475b as class-II gene transcribed by RNA polymerase II. By 5' deletion analysis of Psu-miR475b promoter in a series of promoter-GUS chimeric vectors, we functionally identify three positive regulatory regions and multiple cis-acting elements responsible for Psu-miR475b promoter activity in response to freezing stress and exogenous hormone treatment. Moreover, the Psu-miR475b promoter activity displays a tissue-specific manner, negatively regulated by freezing stress and positively by MeJA, SA or GA treatment. Importantly, we comparatively analyze the time-course transcriptional profiles of Psu-miR475b and its targets in Psu-miR475b over-expression transgenic plants controlled by Psu-miR475b-specific promoter or CaMV 35S constitutive promoter, and explore the regulatory mechanism of Psu-miR475b promoter controlling transcriptional expressions of Psu-MIR475b and its targets in response to freezing stress and exogenous hormone treatment. Our results reveal that Psu-miR475b promoter-mediated transcriptions of Psu-MIR475b and its targets in response to freezing stress may be involved in a cross-talk between freezing response and stress signaling process.

Reduced ubiquitin-specific protease 9X expression induced by RNA interference inhibits the bioactivity of hepatocellular carcinoma cells.

Ubiquitin-specific protease 9X (USP9X) is crucial in many tumor types, but not in hepatocellular carcinoma (HCC). The current study aimed to examine the effects of RNA interference on USP9X expression, and subsequently on the bioactivity of HCC SMMC7721 and HepG2 cells. The protein expression of USP9X in SMMC7721, HepG2 and normal human liver cell line L02 at the cellular level was determined by western blot analysis; USP9X was knocked down by small interfering RNA (siRNA) in HCC SMMC7721 and HepG2 cells. In vitro cell viability was assessed by MTT assay, apoptosis was determined by flow cytometry (FCM) and cell migration was evaluated by Transwell assays. The protein expression of USP9X in SMMC7721 and HepG2 were both significantly higher than that in L02 (P<0.01). The results of western blot demonstrated that the USP9X-siRNA could efficiently inhibit USP9X expression when compared with that of the negative control (NC) group (P<0.01) and MTT assay demonstrated that cell proliferation in USP9X-blocked cells was significantly reduced when compared with that of the NC group (P<0.01). The results of FCM revealed that apoptosis was significantly increased in USP9X-blocked cells when compared with that of the NC group (P<0.01). The results of transwell assay showed that cell migration was significantly inhibited in USP9X-blocked cells when compared with that of the NC group (P<0.01). These results show that expression of USP9X is upregulated in hepatoma cells SMMC7721 and HepG2, and that downregulating USP9X by siRNA may induce cell apoptosis, inhibit cell growth and cell migration in the HCC SMMC7721 and HepG2 cell lines. USP9X may therefore be a potential target for HCC treatment and early detection.