Harnessing Renewable Lignocellulosic Potential for Sustainable Wastewater Purification.

Utilizing renewable lignocellulosic resources for wastewater remediation is crucial to achieving sustainable social development. However, the resulting by-products and the synthetic process characterized by complexity, high cost, and environmental pollution limit the further development of lignocellulose-based materials. Here, we developed a sustainable strategy that involved a new functional deep eutectic solvent (DES) to deconstruct industrial xylose residue into cellulose-rich residue with carboxyl groups, lignin with carboxyl and quaternary ammonium salt groups, and DES effluent rich in lignin fragments. Subsequently, these fractions equipped with customized functionality were used to produce efficient wastewater remediation materials in cost-effective and environmentally sound manners, namely, photocatalyst prepared by carboxyl-modified cellulose residue, biochar-based adsorbent originated from modified lignin, and flocculant synthesized by self-catalytic in situ copolymerization of residual DES effluent at room temperature. Under the no-waste principle, this strategy upgraded the whole components of waste lignocellulose into high-value-added wastewater remediation materials with excellent universality. These materials in coordination with each other can stepwise purify high-hazardous mineral processing wastewater into drinkable water, including the removal of 99.81% of suspended solids, almost all various heavy metal ions, and 97.09% chemical oxygen demand, respectively. This work provided promising solutions and blueprints for lignocellulosic resources to alleviate water shortages while also advancing the global goal of carbon neutrality.

Measuring cell deformation by microfluidics.

Microfluidics is an increasingly popular method for studying cell deformation, with various applications in fields such as cell biology, biophysics, and medical research. Characterizing cell deformation offers insights into fundamental cell processes, such as migration, division, and signaling. This review summarizes recent advances in microfluidic techniques for measuring cellular deformation, including the different types of microfluidic devices and methods used to induce cell deformation. Recent applications of microfluidics-based approaches for studying cell deformation are highlighted. Compared to traditional methods, microfluidic chips can control the direction and velocity of cell flow by establishing microfluidic channels and microcolumn arrays, enabling the measurement of cell shape changes. Overall, microfluidics-based approaches provide a powerful platform for studying cell deformation. It is expected that future developments will lead to more intelligent and diverse microfluidic chips, further promoting the application of microfluidics-based methods in biomedical research, providing more effective tools for disease diagnosis, drug screening, and treatment.

Synthesis of Renewable High-Density Fuel with Vanillin and Cyclopentanone Derived from Hemicellulose.

1,3-bis(cyclohexylmethyl)cyclopentane, a renewable high-density fuel, was first produced in a high overall carbon yield (79.5%) with vanillin and cyclopentanone, which can be derived from biomass. The synthetic route used in this work contains two steps. In the first step, 2,5-bis(4-hydroxy-3-methoxybenzylidene)cyclopentanone was synthesized by aldol condensation of vanillin and cyclopentanone under the catalysis of sulphuric acid. Over the optimized condensation, a high carbon yield (82.6%) of 2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone was achieved at 80 ºC. In the second step, 2,5-bis(4-hydroxy-3-methoxybenzylidene) cyclopentanone was hydrodeoxygenated over the Pd/HY catalyst in cyclohexane as solvent. High carbon yields of 1,3-bis(cyclohexylmethyl)cyclopentane (96.2%) was obtained. The polycycloalkane mixture as obtained has a density of 0.943 g mL-1 and a freezing point of -35 °C. It can be blended into conventional high-density fuels (e.g., JP-10) for rockets and missile propulsion as a potential application.

Transiting Back Home: Caregivers' Lived Experiences in Caring for Loved Ones on the Nasogastric Tube in the Home-Setting in Singapore.

INTRODUCTION: Little is understood about caregivers' lived experiences when first caring for patients on the nasogastric tube at home in an Asian setting. To enhance understanding, our study aimed to chart these caregivers' psycho-emotional evolutions felt during such caregiving experiences in Singapore. METHOD: Utilizing purposive sampling, a descriptive phenomenological study was performed, with semi-structured interviews of 10 caregivers of persons on nasogastric tube feeding conducted. Thematic analysis was utilized. RESULTS: Our findings chart four psycho-emotional transitions of a caregiver's journey in nasogastric tube feeding and the cultural dynamics involved-(a) Disruption of Caregivers' Normality: Attempting to Grasp Reality, (b) Encountering Road-Blocks: Despondency Arises and Frustrations Abound, (c) Adjusting to the New Normal: Reclaiming Confidence and Positivity, (d) Thriving and Integrating into the New Normal, and (e) Cultural Dynamics At Play. DISCUSSION: Our findings illuminate the understanding of caregivers' varying needs, guiding delivery of culturally-congruent caregiver support targeted at each psycho-emotional evolution.

Development of polylactic acid based antimicrobial food packaging films with N-halamine modified microcrystalline cellulose.

Bio-based "green" films with superior antimicrobial activity were developed from polylactic acid (PLA) and cyclic N-halamine 1-chloro-2,2,5,5-tetramethyl-4-imidazolidinone (MC) grafted microcrystalline cellulose (MCC) fibers (herein referred to as g-MCC). The structure of g-MCC was characterized by Fourier Transform Infrared (FT-IR) and Nuclear Magnetic Resonance (NMR) spectroscopy. Results indicated N-halamine MC was successfully grafted onto MCC fibers, with a grafting percentage of 10.24 %. The grafting improved compatibility between g-MCC and PLA, leading to an excellent dispersion of g-MCC in the film matrix, and a superior transparency of the g-MCC/PLA compared to that of the MCC/PLA films. Additionally, the enhanced compatibility the g-MCC/PLA films produced better mechanical properties including mechanical strength, elongation at break and initial modulus than those of both MCC/PLA and MC/PLA composites. With N-halamine, g-MCC/PLA completely inactivated all the inoculated Escherichia coli and Staphylococcus aureus within 5 and 30 min of contact, respectively. More importantly, the migration test showed that the oxidative chlorine of g-MCC/PLA was highly stable than that of MC/PLA films, providing a long-term antimicrobial activity. Finally, preservation test conducted on fresh bread slices further demonstrated its promising applications in the food industry.

Research progress of catalysts for aldol condensation of biomass based compounds.

Research progress of catalysts of the aldol condensation reaction of biomass based compounds is summarized for the synthesis of liquid fuel precursors and chemicals. In summary, an acidic catalyst, alkaline catalyst, acid-base amphoteric catalyst, ionic liquid and other catalysts can catalyze the aldol condensation reaction. The aldol condensation reaction catalyzed by an acid catalyst has the problems of low conversion and low yield. The basic catalyst catalyzes the aldol condensation reaction with high conversion and yield, but the existence of liquid alkali is difficult to separate from the product. The reaction temperature needed for oxide and hydrotalcite alkali is relatively high. The basic resin has good catalytic activity and at a low reaction temperature, and is easy to separate from the target product. Acid-base amphoteric catalysts have received extensive attention from researchers for their excellent activity and selectivity. Ionic liquid is a new type of material, which can also be used for the aldol condensation reaction. In the future application of aldol condensation, the development of strong alkaline resin is a good research direction.

Hyperhubeins A-I, Bioactive Sesquiterpenes with Diverse Skeletons from Hypericum hubeiense.

Nine new sesquiterpenes, hyperhubeins A-I (1-9), and 14 known analogues (10-23) were isolated from the aerial portions of Hypericum hubeiense. Their structures and absolute configurations were determined unambiguously via spectroscopic analysis, single-crystal X-ray diffraction, and electronic circular dichroism calculations. Compounds 1-3 possess an unprecedented sesquiterpene carbon skeleton. Further, a plausible biosynthetic pathway from farnesyl diphosphate (FPP) is proposed. The isolated phytochemicals were evaluated for neuroprotective and anti-neuroinflammatory properties in vitro. Compounds 1, 2, 5-8, 14, and 21 displayed notable neuroprotective activity against hydrogen peroxide (H2O2)-induced lesions in PC-12 cells at 10 µM. Additionally, compounds 1, 2, 12, and 13 exhibited inhibition of lipopolysaccharide (LPS)-induced nitric oxide (NO) production in BV-2 microglial cells, with their IC50 values ranging from 4.92 to 6.81 µM. Possible interactions between these bioactive compounds and inducible nitric oxide synthase (iNOS) were predicted via molecular docking. Moreover, Western blotting indicated that compound 12 exerted anti-neuroinflammatory activity by suppressing LPS-stimulated expression of toll-like receptor-4 (TLR-4) and inhibiting consequent activation of nuclear factor-kappa-B (NF-κB) signaling.

Modeling of Red Blood Cells in Capillary Flow Using Fluid-Structure Interaction and Gas Diffusion.

Red blood cell (RBC) distribution, RBC shape, and flow rate have all been shown to have an effect on the pulmonary diffusing capacity. Through this study, a gas diffusion model and the immersed finite element method were used to simulate the gas diffusion into deformable RBCs running in capillaries. It has been discovered that when RBCs are deformed, the CO flux across the membrane becomes nonuniform, resulting in a reduced capacity for diffusion. Additionally, when compared to RBCs that were dispersed evenly, our simulation showed that clustered RBCs had a significantly lower diffusion capability.

SPAG5 Activates PI3K/AKT Pathway and Promotes the Tumor Progression and Chemo-Resistance in Gastric Cancer.

The sperm-associated antigen 5 (SPAG5) is an important protein in mitosis and cell cycle checkpoint regulation, with more attention as a novel oncogene in various cancers. High level of SPAG5 expression has been detected in our clinical gastric cancer (GC) samples and The Cancer Genome Atlas GC data. However, the bio-function and potential mechanism of SPAG5 in GC remain unclear. In this study, we investigated the role of SPAG5 in GC development and the correlation between SPAG5 and 5-fluorouracil (5-FU) treatment. SPAG5 expression was increased in GC samples compared with that in normal tissues (80.8% vs. 22.0%), which was apparently associated with a worse outcome. Biological experiments showed that knockdown of SPAG5 induced apoptosis and suppressed proliferation in cells and animal models. Downregulation of SPAG5 enhanced the sensitivity of 5-FU in GC cells. Gene microarray chip identified 856 upregulated and 787 downregulated genes in SPAG5 silencing cells. Furthermore, 12 significant genes, including CDKN1A, CDKN1B, EIF4E, MAPK1, and HSP90B1, belonged to the PI3K/AKT signaling pathway using ingenuity pathway analysis. Meanwhile, real-time PCR and Western blotting results showed that knockdown of SPAG5 inhibited PI3K/AKT signaling pathway. Collectively, SPAG5 promotes the growth of GC cells by regulating PI3K/AKT signaling pathway, which could be the promising target gene in GC therapy.

A Sustainable and Antimicrobial Food Packaging Film for Potential Application in Fresh Produce Packaging.

N-halamines are a group of compounds containing one or more nitrogen-halogen covalent bond(s). This high-energy halide bond provides a strong oxidative state so that it is able to inactivate microorganisms effectively. In this study, a sustainable film was developed based on polylactic acid (PLA) with incorporated N-halamine compound 1-chloro-2,2,5,5-tetramethyl-4-imidazolidinone (MC), as a promising antimicrobial food packaging material. Results showed that the incorporation of MC prevented the crystallization of PLA and improved the physical properties of the films. In addition, both the moisture barrier and the oxygen permeability were improved with the presence of MC. Importantly, the antimicrobial film was able to inactivate inoculated microorganisms by a factor of seven log cycles in as little as 5 min of contact. Films that contained higher levels of MC further enhanced the antimicrobial efficacy. Fresh strawberries packed with the fabricated films maintained the quality for up to 5 days. Due to the ease of fabrication and the effective biocidal property, these films have a wide range of potential applications in the field of food packaging to extend the shelf life of fresh produce.

In vitro fecal fermentation properties of polysaccharides from Tremella fuciformis and related modulation effects on gut microbiota.

Tremella fuciformis is an edible and medicinal mushroom. Polysaccharides from T. fuciformis have received increasing attention due to their diversely pharmacological activities. In this study, the digestive behavior and fermentation characteristics of T. fuciformis polysaccharides (TFP) were studied. The results revealed that the reducing sugar content, chemical composition, molecular weight, rheological property, constituent monosaccharide, and FT-IR spectrum of TFP were not altered after the in vitro simulated digestion, indicating that it was indigestible under different simulated digestion conditions. However, the physicochemical characteristics of TFP, including reducing sugar content, molecular weight, constituent monosaccharide, and free monosaccharide released, were obviously altered after the in vitro fermentation for 48 h, indicating that it was remarkably utilized by intestinal microbiota in human feces. Notably, TFP could obviously modulate the microbial composition via promoting the relative abundances of Phascolarctobacterium, Bacteroides, and Lachnoclostridium. Moreover, TFP could also increase the production of short-chain fatty acids, including acetic, propionic, n-butyric, and n-valeric acids, after the in vitro fermentation for 48 h. These results showed that TFP was stable under the simulated digestion conditions, but could be utilized by intestinal microbiota in human feces, and might possess the potential to improve intestinal health.

Knockdown of GPRC5B alleviates the high glucose-induced inflammation and extracellular matrix deposition of podocyte through inhibiting NF-κB pathway.

BACKGROUND: Diabetes is a serious disease that could greatly increase the risk of cardiovascular complications, whereas the underlying pathology of DN is still unknown. GPRC5B is a member of the RAIG subfamily of type 3 (family C) GPCR, and its role in DN is still unclear. OBJECTIVE: To unveil the role of GPRC5B in diabetic nephropathy (DN) progression and investigate the potential signaling pathway. MATERIALS AND METHODS: Podocytes were stimulated with high glucose and expression of GPRC5B was analyzed by qPCR and western blot. Then the level of GPRC5B was depleted by siRNA transfection and inflammatory cytokine level was monitored by ELISA assay. The ECM depostion and the activation of NF-κB pathway were detected by Immunoblot. RESULTS: We investigated the possible role of GPRC5B in the pathology of diabetic nephropathy. We found GPRC5B was highly expressed in high glocuse (HG) induced podocytes. The depletion of GPRC5B inhibited HG induced cell inflammation. In addition, the ablation of GPRC5B suppressed the HG induced ECM deposition. We further found GPRC5B could alleviate the inflammation and extracellular matrix deposition of HG-induced podocytes through NF-κB pathway. CONCLUSION: We therefore thought GPRC5B could serve as a promising target for the treatment of diabetic nephropathy. G-protein-coupled receptors.

Antitumor effects of cadmium against diethylnitrosamine-induced liver tumors in mice.

Cadmium (Cd) has been reported to exhibit antitumor effects against chemically induced liver tumors. However, the antitumor effects of Cd are not completely understood. Metallotherapy, the use of a toxic metal to attack liver tumors, could be a viable strategy. In the present study, 8-week old, male, C57BL/6 mice were administered injections of diethylnitrosamine (DEN) (90 mg/kg, and then 50 mg/kg 2 weeks later), followed by liver tumor promotion with carbon tetrachloride. Cadmium chloride was administered in the drinking water (1000 ppm) from 21-40 weeks after DEN initiation. Body weights were recorded and liver tumor formation was monitored via ultrasound. At the end of experiments, livers were removed, weighed, and the tumor incidence, tumor numbers and tumor size scores were recorded. Liver histology and metallothionein (MT) immunostaining were performed. After DEN injection, animal body weight decreased, and then slowly recovered with time. Cd treatment did not affect animal body weight gain. Ultrasound analysis detected liver tumors 35 weeks after DEN injection, and the mice were necropsied at 40 weeks. Liver/body weight ratios increased in the DEN and DEN + Cd groups. Cd treatment decreased the tumor incidence (71 vs. 17%), tumor numbers (15 vs. 2) and tumor scores (22 vs. 3) when compared with the DEN only group. Histopathology showed hepatocyte degeneration in all groups, and immunohistochemistry showed MT-deficiency in the liver tumors, while MT staining was intensified in the surrounding tissues. Reverse transcription-quantitative PCR showed increases in α-fetoprotein level in DEN-treated livers, and increases in MT-2 and tumor necrosis factor α (TNFα) levels in Cd-treated livers. Thus, it was concluded that Cd is effective in the suppression of DEN-induced liver tumors, and that the mechanisms may be related to MT-deficiency in tumors and the induction of TNFα to kill tumor cells.

A novel mouse model simulating transurethral laser vaporization prostatectomy.

Benign prostatic hyperplasia (BPH) is a common disease in elderly men, and transurethral laser prostatectomy (TULP) has been widely used in the clinic to remove bladder outlet obstruction caused by BPH. Previous animal models for wound repair after prostatectomy have many limitations, and there have been no previous reports of a mouse model of TULP. Therefore, this study aimed to establish a novel mouse model of TULP. Twelve healthy adult Kunming (KM) mice received transurethral laser vaporization prostatectomy with a 200-µm thulium laser. The mice were sacrificed, and wound specimens from the prostatic urethra and bladder neck were harvested at 1 day, 3 days, 5 days, and 7 days after surgery. Hematoxylin-eosin (HE) and immunohistochemistry were applied to confirm the establishment of the mouse TULP model. One day after the surgery, urothelium expressing uroplakin (UPK) was absent in the urethral wound site, and a large number of necrotic tissues were found in the wound site. There was no UPK-positive urothelium in the wound 3 days after surgery. At 5 days after surgery, monolayer urothelium expressing UPK was found in the wound site, indicating that the re-epithelization of the wound had been completed. On the 7th day after surgery, there were multiple layers of urothelium with UPK expression, indicating that the repair was completed. It is feasible to establish a mouse TULP model by using a microcystoscope system and a 200-µm thulium laser.

Rapid Detection of Adulteration in Dendrobium Huoshanense with Dendrobium Henanense by ATR-FTIR Combined with Multivariate Methods.

Dendrobium huoshanense (DHS) has long been used to make tea drink, soup, and porridge to protect eye and liver in many Southeast Asian countries for centuries. As a rare and endangered functional food, adulteration in DHS with visually similar but cheaper and more accessible plants such as Dendrobium henanense (DHN) because of their similarities in morphology has become prevalent in the market. In this study, the Attenuated Total Reflectance Fourier transform Infrared Spectroscopy (ATR-FTIR) combined with chemometric methods was established to detect fraudulent addition in DHS with DHN. The partial least squares (PLS) models based on the ATR-FTIR files of DHS mixed with different proportions of DHN were built under cross validation and tested with different independent data sets. To reduce the variables' lack of information and increase the accuracy of the model, different wavelength selection methods including Moving Window Partial Least Squares (MW-PLS), Monte Carlo-uninformative variable elimination (MC-UVE), and interval random frog (iRF) were compared.The results showed that iRF performed the most perfectly with the number of latent variables (nLVs = 7), the lowest Root Mean Square Error of Cross-Validation (RMSECV = 7.37), and the maximum determination coefficients (R2 = 0.9721). The excellent performance of the model was proved by the low RMSEP value of 6.44% and the high R2 value of 0.9556. The developed method could rapidly quantify the adulteration DHN in DHS, and our study might provide an efficient and great potential technique tool for the rapid, green, low-cost, and nondestructive identification and quantification for DHS adulterated with DHN.

Simultaneous Quantification of 11 Phenolic Compounds and Consistency Evaluation in Four Dendrobium Species Used as Ingredients of the Traditional Chinese Medicine Shihu.

The interchangeable use of different herbs to prepare the same formulation is a common practice in Traditional Chinese Medicine (TCM). However, this practice would require the component herbs to share similar compositions, at least in terms of the bioactive agents, to ensure they can replace each other in drug preparation. In this study, we developed an effective and comprehensive high-performance liquid chromatography-diode array detector (HPLC-DAD) method for simultaneous analysis of 11 phenolic compounds in the methanol extracts of Dendrobium huoshanense, Dendrobium nobile (D. nobile), Dendrobium chrysotoxum (D. chrysotoxum), and Dendrobium fimbriatum (D. fimbriatum), which have been identified as interchangeable ingredients for the same TCM preparation "Shihu" in the Chinese pharmacopeia (ChP). The consistency of the four Dendrobium species was evaluated on the basis of the presence of the 11 investigated compounds and the HPLC fingerprints of the methanol extracts of the plants. When gradient elution was performed with a solvent system of acetonitrile and water on a Zorbax Eclipse XDB-C18 (150 mm × 4.6 mm, 5 µm) with monitoring at 220 nm, all 11 investigated compounds were isolated at the baseline. The established HPLC method showed excellent linearity (all analytical curves showed relative coefficients [R2] > 0.999), sensitivity, precision (relative standard deviation [RSD] < 2%), and accuracy (recovery, 90.65-99.17%). These findings confirmed that the method we constructed was reliable. Quantification analysis showed significant differences in the contents of the investigated polyphenols in the four Dendrobium species. Evaluations of consistency revealed that the similarities among the four species were 0.299-0.906 in assessments based on the 11 polyphenols and 0.685-0.968 in assessments based on HPLC fingerprints. Thus, the components of the four Dendrobium species may be significantly different, and more experiments are required to determine whether they can be used interchangeably in the same amounts for preparing the formulation according to ChP.

Clinical Inertia and 2-Year Glycaemic Trajectories in Patients with Non-Newly Diagnosed Type 2 Diabetes Mellitus in Primary Care: A Retrospective Cohort Study.

OBJECTIVE: To analyse diabetes treatment, treatment change and self-management behaviours in association with 2-year glycaemic trajectories in patients with non-newly diagnosed type 2 diabetes mellitus in Chinese primary care. METHODS: This was an observational, multi-centre, longitudinal, retrospective cohort study. Clinical data of 4690 subjects were extracted from electronic medical records, including serial glycated haemoglobin A1c (HbA1c) measurements, antidiabetic medication records and compliance to exercise, diet, medications and self-monitoring of blood glucose (SMBG). Patterns of longitudinal HbA1c trajectories were identified using the percentage of HbA1c measurements <7.5% from the second available HbA1c measurement. Clinical relevance of the clusters was assessed through multivariable analysis. RESULTS: Approximately half of the participants demonstrated good glycaemic control; of these, 34.5% demonstrated stable, good control, and 13.7% demonstrated relatively good control. About 16.2% demonstrated moderate control, and 35.6% demonstrated poor control. From the good to poor control groups, the percentage of subjects treated with insulin at baseline and during the follow-up period increased gradually, while the percentage of subjects adhering to exercise, diet, medications and SMBG decreased gradually. Compared with baseline, the adherence to exercise, diet, medications and SMBG improved significantly. Approximately 50% and 26% of subjects in the two poorest control groups, respectively, experienced treatment changes. After multivariable adjustments, baseline HbA1c ≥7.5%, HbA1c change ≥-0.5% from baseline to visit 1, insulin treatment, treatment change, poor adherence to diet, exercise, SMBG during the follow-up period and HbA1c measurements <3 per year were significantly associated with poorer glycaemic control. CONCLUSION: We identified four longitudinal HbA1c trajectories in patients with non-newly diagnosed type 2 diabetes. Even if baseline HbA1c is suboptimal, aggressive treatment changes, good adherence during the follow-up period, ≥3 HbA1c measurements per year and reducing HbA1c levels to a certain extent by the first follow-up visit were important for good, stable, long-term glycaemic control.

Simultaneous analysis of 20 free amino acids by a single marker combined with an HPLC fingerprint evaluation of Dendrobium huoshanense.

A phenylhexyl isothiocyanate (PITC) precolumn derivatization quantitative analysis of multicomponents by a single marker (QAMS) strategy for the simultaneous analysis of 20 free amino acids (FAA) in Dendrobium huoshanense is proposed. The method was validated by the linearity, limit of detection (LDO), and limit of quantitation (LOQ), recovery, precision, and stability. The results showed that when applying the established method, the LOQ of the FFAs was lower than 1 ng/ml except threonine (1.32 ng) and cysteine (1.16 ng). The QAMS investigation revealed that, using any one of the 20 FAAs as the reference internal standard, no significant differences were observed between the external standard method and the QAMS method for the quantification of FAAs in D. huoshanense by PITC precolumn derivatization [The relative standard deviation (RSD, %) by QAMS and ESM were all below 5%]. HPLC fingerprint investigation combined with similar analysis (the similarity values for S1-S25 were >0.875) and quality fluctuation analysis showed that the cultivation environment might have a great effect on the accumulation of FAAs in D. huoshanense. Overall, our study showed that we might increase the accuracy and scope of the simultaneous quantification of multicomponents using the QAMS technique by being derivatized with a strong UV absorbing group, and QAMS combined with chromatographic fingerprinting can be considered good quality criteria for the quality control of D. huoshanense and may provide analytical technical support for research on Maillard Reaction during the further processing of D. huoshanense.

MUC1 Promotes Mesangial Cell Proliferation and Kidney Fibrosis in Diabetic Nephropathy Through Activating STAT and ß-Catenin Signal Pathway.

Diabetic nephropathy (DN) is a complication of diabetes, which leads to most end-stage kidney diseases and threatens health of patients. Mucin 1 (MUC1) is a heterodimeric oncoprotein, which is abnormally expressed in tumors and hematologic diseases. The aim of this study is to clarify the mechanism and role of MUC1 in DN. The mesangial cells (MCs) suffered from high glucose (HG) treatment to mimic DN in vitro. The cell proliferation was detected by Cell Counting Kit-8 assay and 5-ethynyl-2-deoxyuridine (EdU) staining assay. The expression of MUC1 and fibrosis markers: fibronectin, collagen I, and collagen IV were assessed by western blot. In this study, we demonstrated that HG treatment induced MUC1 expression in MCs. With knockdown of MUC1 or overexpressed MUC1 in MCs, the results indicated that knockdown of MUC1 inhibited MCs proliferation and reduced kidney fibrosis markers expression, including fibronectin, collagen I, and collagen IV, whereas overexpression of MUC1 led to opposite results. Mechanically, MUC1 activated signal transducers and activators of transcription (STAT) and ß-catenin signal pathway. After added AG490 (STAT inhibitor) or FH535 (ß-catenin inhibitor), blocking STAT3 and ß-catenin signal pathway attenuated MUC1-induced cell proliferation and fibronectin production in MCs. Finally, knockdown of MUC1 attenuated DN-induced kidney fibrosis in db/db mice. Therapeutic target for DN. In conclusion, MUC1 promotes MCs proliferation and kidney fibrosis in DN through activating STAT and ß-catenin signal pathway, which can help to provide a novel therapeutic target for DN.

Podofilox suppresses gastric cancer cell proliferation by regulating cell cycle arrest and the c-Myc/ATG10 axis.

Gastric cancer (GC) is a malignancy for which effective therapeutic drugs are limited. Podofilox exhibits antitumor effects in various types of cancer; however, whether it may inhibit GC growth remains unknown. The aim of the present study was to investigate the role of podofilox in GC. Cell Counting Kit-8, colony formation and cell cycle assays were used to detect the role of podofilox on cellular proliferation and the cell cycle, respectively. A microarray was used to detect the transcriptional changes induced by podofilox in GC cells. The results of the present study demonstrated that podofilox inhibited GC cell proliferation and colony formation. The half maximal inhibitory concentration of podofilox in AGS and HGC-27 cells was 2.327 and 1.981 nM, respectively. In addition, treatment with podofilox induced G0/G1 cell cycle arrest. Molecular analysis based on microarray data demonstrated that podofilox altered the expression levels of genes involved in the cell cycle, c-Myc and p53 signaling. Autophagy-related 10 (ATG10), which was highly expressed in GC tissues, was also downregulated by podofilox, as demonstrated by the results of the microarray analysis and immunoblotting. To determine the involvement of ATG10 in GC, ATG10 was knocked down in GC cells by small interfering RNA, which suppressed the proliferation and colony formation of GC cells compared with those observed in the control-transfected cells. Taken together, the results of the present study suggested that podofilox may inhibit GC cell proliferation by preventing the cell cycle progression and regulating the c-Myc/ATG10 signaling pathway.