Manganese dioxide decorated kiwi peel powder for efficient removal of lead from aqueous solutions, blood and Traditional Chinese Medicine extracts.

For human health and environment safety, it is of great significance to develop novel materials with high effectiveness for removal of lead from not only aqueous solutions but also human body and traditional Chinese medicines. Here, functional kiwi peel composite, manganese dioxide decorated kiwi peel powder (MKPP), is proposed for the removal of Pb2+ effectively. The adsorption of Pb2+ in aqueous solution is a highly selective and endothermic process and kinetically follows a pseudo-second-order model, which can reach equilibrium with the capacity of 192.7 mg/g within 10 min. Comprehensive factors of hydration energy, charge-to-radius ratio and softness of Pb2+ make a stronger affinity between MKPP and Pb2+. The possible adsorption mechanism involves covalent bond, electrostatic force and chelation, etc. MKPP can be efficiently regenerated and reused with high adsorption efficiency after five cycles. Besides, MKPP can remove over 97% of Pb2+ from real water samples. MKPP can also alleviate lead poisoning to a certain extent and make the Pb level of TCM extract meet the safety standard. This work highlights that MKPP is a promising adsorbent for the removal of Pb2+ and provides an efficient strategy for reusing kiwi peel as well as dealing with the problem of Pb pollution.

Comparison of Salvianolic Acid A Adsorption by Phenylboronic-Acid-Functionalized Montmorillonites with Different Intercalators.

Due to its success in treating cardio-cerebrovascular illnesses, salvianolic acid A (SAA) from Salvia miltiorrhiza is of major importance for effective acquisition. For the adsorption of salvianolic acid, cationic polyelectrolytes, and amino-terminated silane intercalated with phenylboronic-acid-functionalized montmorillonites, known as phenylboronic-acid-functionalized montmorillonites with PEI (PMP) and phenylboronic-acid-functionalized montmorillonites with KH550 (PMK), respectively, were produced. In this paper, detailed comparisons of the SAA adsorption performance and morphology of two adsorbents were performed. PMP showed a higher adsorption efficiency (>88%) over a wide pH range. PMK showed less pH-dependent SAA adsorption with a faster adsorption kinetic fitting in a pseudo-second-order model. For both PMP and PMK, the SAA adsorption processes were endothermic. Additionally, it was clearer how temperature affected PMP adsorption. PMK has a higher adsorption selectivity. This study demonstrates how the type of intercalator can be seen to have an impact on adsorption behavior through various structural variations and offers an alternative suggestion for establishing a dependable method for the synthesis of functional montmorillonite from the intercalator's perspective.

Total flavonoids from the dried root of Tetrastigma hemsleyanum Diels et Gilg inhibit colorectal cancer growth through PI3K/AKT/mTOR signaling pathway.

The dried root of Tetrastigma hemsleyanum Diels et Gilg is used as a traditional Chinese medicine in southern China, as a folk remedy for carcinomas and gastrointestinal diseases. The total flavonoids of T. hemsleyanum (THTF) provide its main bioactive constituents. However, the mechanisms underlying its potential activity on colorectal cancer are still unknown. Here, we investigated the antitumor effect of THTF on colorectal cancer in vitro and in vivo. It was found that THTF inhibited HCT-116 and HT-29 cell growth, with an IC50 of 105.60 and 140.80 µg/mL, respectively. THTF suppressed clonogenicity and promoted apoptosis in HCT-116. In vivo, THTF (120 mg/kg) delayed tumor growth in HCT-116 xenografts without influencing on body weight, organ pathology and indexes, and blood routine level. Mechanistically, THTF inhibited the expression of PI3K, AKT, and mTOR at the protein level and transcriptional levels. Molecular docking indicated eight compounds in THTF (kaempferol 3-rutinoside, rutinum, isoquercitrin, L-epicatechin, quercetin, astragalin, kaempferol 3-sambubioside, and catechin) strongly bound with amino acid sites of PI3K and mTOR proteins, indicating a high affinity. The results suggest that THTF delayed colorectal tumor growth by inhibiting the PI3K/AKT/mTOR pathway and might be a potential candidate for colorectal cancer prevention.

Tree growth response of Fokienia hodginsii to recent climate warming and drought in southwest China.

To date, few attempts have been made to assess the influence of climate change on forest ecosystems and on the relationship between tree growth and climate in humid areas of low latitudes. In this paper, we studied the response of tree growth and forest ecosystem to climate change by using Fokienia hodginsii tree-ring cores from the northern Yunnan-Guizhou Plateau, southwest of China. Tree growth correlates the highest (r = -0.64, p < 0.01) with mean temperature (July-September), but the coefficients were changing with time as revealed by a moving correlation analysis. Tree growth is significantly (p < 0.05) and positively correlated with January-April mean temperature from AD 1961-1987, while correlations with precipitation are insignificant. In contrast, from 1988 to 2014, tree growth correlated negatively with mean temperature of previous summer and positively with precipitation of previous August-September. This indicated that the limiting factors for tree growth have changed under different climate conditions. The meteorological data suggested that from 1961 to 1987 it was cold and wet in the study area and radial growth is limited by winter and spring temperatures. This restriction is weaker if the climate is appropriate in general. However, from 1988 to 2014, the combined effects of recent warming and decreasing precipitation have led to an increasing response of tree-ring width to drought. In addition, a large proportion of mature F. hodginsii mortality occurred from 2007 to 2013, which corresponds with a drastic reduction of radial growth (narrowest in recent 100 years). The recent drought, induced by decreasing precipitation and increasing temperature, may have passed the threshold which F. hodginsii could tolerate, causing tree growth reduction, tree growth-climate relationship change, as well as catastrophic tree mortality. All these changes may lead to further responses of the local ecosystem to climate change which should be highly regarded.

Fine-tuning of liposome integrity for differentiated transcytosis and enhanced antitumor efficacy.

Transcytosis-inducing nanomedicines have been developed to improve tumor extravasation. However, the fate during transcytosis across multicell layers and the structural integrity of the nanomedicines before reaching tumor cells could impact antitumor therapy. Here, a BAY 87-2243 (a hypoxia-inducible factor-1 inhibitor)-loaded liposomal system (HA-P-LBAY) modified by low molecular weight protamine (LMWP) and crosslinked by hyaluronic acid (HA) was constructed. This system could accomplish differentiate cellular transport in endothelial and tumor cells by fine-tuning its structural integrity, i.e. transcytosis across the endothelial cells while preserving structural integrity, facilitating subsequent retention and drug release within tumor cells via degradation-induced aggregation. In vitro cellular uptake and transwell studies demonstrated that HA-P-LBAY were internalized by endothelial cells (bEnd.3) via an active, caveolin and heparin sulfate proteoglycan (HSPG)-mediated endocytosis, and subsequently achieved transcytosis mainly through the ER/Golgi pathway. Moreover, the fluorescence resonance energy transfer (FRET) study showed that HA-crosslinking maintained higher integrity of HA-P-LBAY after transcytosis, more efficiently than electrostatic coating of HA (HA/P-LBAY). In addition, more HA-P-LBAY was retained in tumor cells (4T1) compared to HA/P-LBAY corresponding to its enhanced in vitro cytotoxicity. This may be attributed to better integrity of HA-P-LBAY post endothelial transcytosis and more degradation of HA in tumor cells, leading to more liposome aggregation and inhibition of their transcytosis, which was inferred by both TEM images and the HAase responsiveness assay proved by FRET. In vivo, HA-P-LBAY exhibited more potency in tumor suppression than the other formulations in both low and high permeability tumor models. This highlighted that fine-tuning of structural integrity of nanocarriers played a key role no matter whether the transcytosis of nanocarriers contributed to cellular transport. Collectively, this study provides a promising strategy for antitumor therapies by fine-tuning liposome integrity to achieve active trans-endothelial transport with structural integrity and selective aggregation for prolonged tumor retention.

Physical Stability of Lotus Seed and Lily Bulb Beverage: The Effects of Homogenisation on Particle Size Distribution, Microstructure, Rheological Behaviour, and Sensory Properties.

The lotus seed and lily bulb beverage (LLB) has a problem with solid particle sedimentation. To address this issue, LLB was homogenised twice at different pressures (0~100 MPa) using a homogeniser. This study aims to investigate the changes in the particle size distribution (PSD), microstructure, rheological behaviour, sedimentation index (IS), turbidity, physicochemical properties, and sensory quality of LLBs after homogenisation treatments. The results regarding PSD and microstructure showed that the suspended particles were decomposed at high pressure with increasing homogenisation pressure, forming small particles of cellular material, cell wall fragments, fibre fractions, and polymers. The LLB showed shear-thinning behaviour and weak gelation characteristics (G' > G″) and rheological properties. Among all homogenisation pressures, the 60 MPa sample showed the lowest sedimentation rate and the highest turbidity. When the pressure was increased from 0 to 100 MPa, the total soluble solid (TSS) content showed an upward trend, while the ascorbic acid content (AAC) gradually decreased. The highest sensory evaluation was observed in the 60 MPa sample in terms of overall acceptability.

Effects of Thermosonication on the Antioxidant Capacity and Physicochemical, Bioactive, Microbiological, and Sensory Qualities of Blackcurrant Juice.

This study investigated the effects of thermosonication (TS) on the quality of blackcurrant juice, along with its physicochemical properties, bioactive compounds, antioxidant capacity, and microbiological and sensory qualities. The treatments included raw juice (RJ), pasteurized juice (90 °C, 1 min, PJ), and thermosonicated juice (480 W, 40 kHz at 40, 50, or 60 °C, for 10, 20, 30, or 40 min, TJ). The results indicated that the effects of pasteurization and thermosonication on the pH, total soluble solids, and titratable acidity of the juice were not significant (p > 0.05). However, the cloudiness, browning index, and viscosity were significantly increased (p < 0.05), and the color properties of the blackcurrant juice were improved. The total phenolic, flavonoid, and anthocyanin contents of TJ (treated at 50 °C for 30 min) were increased by 12.6%, 20.9%, and 40.4%, respectively, and there was a notable decline in ascorbic acid content after the pasteurization treatment, while the loss was minor in all TJ samples compared with RJ. The scavenging ability of 1,1-diphenyl-2-pyridyl and hydroxyl radicals increased to 52.77% and 50.52%, respectively, which were significantly (p < 0.05) higher than those in the RJ and PJ samples. In addition, both pasteurization and thermosonication resulted in a significant (p < 0.05) reduction in microbial counts, while there were no significant (p > 0.05) differences in the sensory parameters compared with the RJ samples. In conclusion, this study suggests that TS is an effective method that can be used as an alternative to pasteurization to improve the quality of blackcurrant juice.

Magnetic resonance imaging characteristics of primary intraspinal peripheral primitive neuroectodermal tumour.

PURPOSE: The purpose of our study was to describe the salient magnetic resonance imaging (MRI) findings in primary intraspinal peripheral primitive neuroectodermal tumour (PNET). METHODS: A retrospective review of the clinical and MRI images of 7 pathologically proven cases of intraspinal peripheral PNETs was performed. The various parameters, such as vertebral level of involvement; tumour location, size, focality, and margin; signal intensity of the lesion; the presence of hemorrhage or calcification; any signal voids; assessment of the adjacent cord for cord compression; cord dilatation; the presence of paraspinal tissue mass; or vertebral or other bony changes, were analysed. RESULTS: All 7 patients had lesions in the thoracolumbar region. Three patients had extradural lesions, 4 had intradural extramedullary lesions, and none had intramedullary lesions. Six lesions were well circumscribed. Only 1 patient had multifocal involvement. All lesions were of hypointense or isointense signal on T1-weighted imaging, whereas all but one were hyperintense on T2-weighted imaging. Lesions enhanced heterogeneously except 1 intradural extramedullary lesion, which enhanced homogeneously. A paraspinal mass was noticed in 2 patients. Vertebral collapse was present in 1 patients. CONCLUSION: Intraspinal peripheral PNETs are rare spinal tumours. Although imaging characteristics are not specific, a focal circumscribed lesion in a young individual at the intramedullary, extramedullary intradural, or extradural spinal location that shows hypointense and hyperintense signal on T1- and T2-weighted images, respectively, requires PNET to be considered in the differentials.

Surface Wind Speed Changes and Their Potential Impact on Wind Energy Resources Across China During 1961-2021.

Enabling the rational use of energy and the realization of the "dual carbon goals" across China will require systematic analysis of temporal and spatial changes in surface wind speed (SWS), determination of key factors influencing SWS, and quantification of wind energy resources. We investigated changes of SWS and their potential impact on wind energy resources using daily SWS data from meteorological observations and based on wind power density (WPD) across China during 1961-2021. The SWS changes were related to atmospheric circulation, surface friction (urbanization and vegetation changes), aerosol emissions and the replacement of observation instruments. The increase of SWS after 2015 was closely related to changes of atmospheric circulation that were reflected by changes of Asian Meridional Circulation Index, North Atlantic Oscillation, and Arctic Oscillation. Compared with the mean SWS, the extreme SWS exhibited a more obvious downward trend and earlier abrupt change. The annual mean SWS decreased by 16.80% in the last six decades, resulting in a decrease of 47.78% in wind energy potential. Regions with annual WPD more than 100 W · m-2 were mainly in western China, northeastern China, northwestern China and some coastal areas. The WPD decreased mainly in northeastern China, northern China, and some coastal areas during the last six decades; it increased mainly in western China. Regions with annual WPD more than 100 W · m-2 and robust coefficient of variation less than 0.5 are high-quality wind energy resource areas and were found mainly in western China, northern China, northeast China, and coastal areas.

Efficacy of kangfuxin liquid on radiotherapy-induced oral mucositis for patients with head and neck squamous cell carcinoma and its effect on salivary glands and immune function.

OBJECTIVE: To observe the efficacy of Kangfuxin liquid on radiotherapy-induced oral mucositis for patients with head and neck squamous cell carcinoma and its effects on salivary glands and immune function. METHODS: A total of 97 patients with head and neck squamous cell carcinoma receiving radiotherapy in Guigang City People's Hospital from January 2019 to June 2021 were retrospectively analyzed and divided into a control group and a test group according to different treatment plans. The two groups received the same radiation therapy. Patients in the control group (n=46) were given borax-containing gargles, while those in the test group (n=51) were treated with Kangfuxin liquid. We observed the incidences and grades of oral mucositis and oral pain, changes in saliva flow rate, pH of saliva, levels of epidermal growth factor (EGF) and amylase, levels of CD4+/CD8+, CD19+/CD69+ and natural killer (NK) cells, and serum cytokine (TGF-ß1, IL-6 and C-reactive protein (CRP)) levels in the two groups before radiotherapy, and after 21 d and 42 d of radiotherapy. Quality of Life Instruments for Cancer Patients-Head and Neck Cancer (QLICP-HN) scores were compared in both groups before radiotherapy, and after 42 d of radiotherapy. RESULTS: No oral mucositis or oral pain was found before radiotherapy in both groups. The incidences of oral mucositis and oral pain after 21 d and 42 d of radiotherapy in the test group were not significantly different from those in the control group (all P>0.05). The grades of oral mucositis and oral pain in the test group after 21 d and 42 d of radiotherapy were lower than those in the control group (all P<0.05). The test group had higher saliva flow rate, pH of saliva, levels of EGF and amylase, and levels of CD4+/CD8+, CD19+/CD69+ and NK cells. The test group had lower serum levels of TGF-ß1, IL-6, and CRP than the control group after 21 d and 42 d of radiotherapy (all P<0.05). The scores of each item of the QLICP-HN scale and total scores in the test group were higher than those of the control group after 42 d of radiotherapy (all P<0.05). CONCLUSION: Kangfuxin liquid effectively prevents the occurrence of radiotherapy-induced oral mucositis for patients with head and neck squamous cell carcinoma, reduces oral mucosal reactions and oral pain, improves salivary gland function, reduces inflammatory response, promotes cellular immune function, improves quality of life, and improves prognosis.

Bioinspired sandwich-like hybrid surface functionalized scaffold capable of regulating osteogenesis, angiogenesis, and osteoclastogenesis for robust bone regeneration.

Recently, strategies that focus on biofunctionalized implant surfaces to enhance bone defect healing through the synergistic regulation of osteogenesis, angiogenesis, and osteoclastogenesis have attracted increasing attention in the bone tissue engineering field. Studies have shown that the Wnt/ß-catenin signaling pathway has an imperative effect of promoting osteogenesis and angiogenesis while reducing osteoclastogenesis. However, how to prepare biofunctionalized bone implants with balanced osteogenesis, angiogenesis, and osteoclastogenesis by activating the Wnt/ß-catenin pathway has seldom been investigated. Herein, through a bioinspired dopamine chemistry and self-assembly method, BML-284 (BML), a potent and highly selective Wnt signaling activator, was loaded on a mussel-inspired polydopamine (PDA) layer that had been immobilized on the porous beta-tricalcium calcium phosphate (ß-TCP) scaffold surface and subsequently modified by a biocompatible carboxymethyl chitosan hydrogel to form a sandwich-like hybrid surface. ß-TCP provides a biomimetic three-dimensional porous microenvironment similar to that of natural cancellous bone, and the BML-loaded sandwich-like hybrid surface endows the scaffold with multifunctional properties for potential application in bone regeneration. The results show that the sustained release of BML from the sandwich-like hybrid surface significantly facilitates the adhesion, migration, proliferation, spreading, and osteogenic differentiation of MC3T3-E1 cells as well as the angiogenic activity of human umbilical vein endothelial cells. In addition to osteogenesis and angiogenesis, the hybrid surface also exerts critical roles in suppressing osteoclastic activity. Remarkably, in a critical-sized cranial defect model, the biofunctionalized ß-TCP scaffold could potentially trigger a chain of biological events: stimulating the polarization of M2 macrophages, recruiting endogenous stem cells and endothelial cells at the injury site to enable a favorable microenvironment for greatly accelerating bone ingrowth and angiogenesis while compromising osteoclastogenesis, thereby promoting bone healing. Therefore, these surface-biofunctionalized ß-TCP implants, which regulate the synergies of osteogenesis, angiogenesis, and anti-osteoclastogenesis, indicate strong potential for clinical application as advanced orthopedic implants.

Expression of miR-92a, miR-224 and miR-25 in non-small cell lung cancer and their correlation with clinical characteristics.

OBJECTIVE: To analyze the correlation of the expression of microRNA-92a (miR-92a), microRNA-224 (miR-224), and microRNA-25 (miR-25) in non-small cell lung cancer with its clinical characteristics. METHODS: This prospective study was performed in 125 non-small cell lung cancer patients admitted to our hospital between January 2019 and January 2020. All patients' cancer and adjacent tissue were collected and the expression of miR-92a, miR-224, and miR-25 were detected using real-time fluorescence quantitative RT-PCR. Data were analyzed using SPSS statistical software (version 20.0). Correlation analysis was conducted using Pearson correlation coefficient. RESULTS: Compared with adjacent tissue, the relative expression of miR-92a, miR-224, and miR-25 in cancer tissue were increased (all P<0.001). There was no correlation between the expression of miR-92a, miR-224, and miR-25 and baseline data like gender, age, smoking history, and tumor size (all P>0.05). The relative expression of miR-92a, miR-224 and miR-25 in differentiated cancer patients were higher than those in highly and moderately differentiated cancer patients (all P<0.05). The relative expression of miR-92a, miR-224 and miR-25 in patients with lymph node metastasis (LNM) were increased when compared with those had no LNM (all P<0.001). Compared with stage I and II patients, the relative expression of miR-92a, miR-224 and miR-25 in stage III and IV patients were increased (all P<0.001). The relative expression of miR-92a, miR-224, and miR-25 were positively correlated to each other (all P<0.01). CONCLUSION: miR-92a, miR-224, and miR-25 are overexpressed in non-small cell lung cancer and the expressions are related to the degree of differentiation, presence or absence of LNM, and TNM staging. In addition, the expression of miR-92a, miR-224 and miR-25 are positively correlated to each other. This suggests that miR-92a, miR-224, and miR-25 cooperatively participated in the occurrence and development of non-small cell lung cancer.

Fritillaria thunbergii Miq. (Zhe Beimu): A review on its traditional uses, phytochemical profile and pharmacological properties.

Fritillaria thunbergii Miq. (Zhe beimu) ranked as oldest known homeopathic traditional folk medicine in China. The bulbs are medicinally important curing cough, inflammation, gastric ulcers, hypertension, diarrhea, and bronchitis. The aim of this review is to enlighten the deeper knowledge about F. thunbergii giving a comprehensive overview on its traditional uses, phytochemistry and pharmacology for future investigation of plant-based drugs and therapeutic applications. Total 48 medicinally important species of Fritillaria were described; total 122 compounds have been identified as results only 72 chemical constituents were described with proper chemical and biological details. F. thunbergii and its bulbs mainly constitute alkaloids, essential oils, diterpenoids, carbohydrates, sterols, amino acids, nucleosides, fatty acids, and lignans. The pharmacological studies demonstrate that F. thunbergii and its bulbs displays a wide range of bioactivities e.g., anti-inflammatory, anticancer, antitussive, expectorant, anti-ulcer, antimicrobial, antioxidant, anti-thyroid, regulation of blood rheology, anti-diarrhea, neuroprotection, and analgesic effects. Although promising reports on the various chemical bioactive constituents and biological properties of F. thunbergii have been published, very few reviews are related specifically to the traditional uses, phytochemistry and pharmacological applications. Further, various other studies on these plants should deserve our more attention for future investigation for drug development and its therapeutic applications.

Skipped multifocal extensive spinal tuberculosis involving the whole spine: A case report and literature review.

RATIONALE: Skipped multifocal extensive spinal tuberculosis (TB) involving the whole spine is very rare. So far, only 3 cases have been reported. PATIENT CONCERNS: We report a rare case of skipped multifocal extensive TB involving the whole spine of a 33-year-old Chinese male. The patient had been asymptomatic until his symptom was significantly aggravated, which caused him to have difficulty in walking and sleeping. The whole spinal computed tomography (CT) scan showed multifocal worm-eaten and osteolytic bony destruction spread over noncontiguous multilevel vertebral involvement in cervical, thoracic, lumbar, and sacral. In addition, the patient presented with low back pain, progressive fever, night sweats, and weight loss. An open biopsy was undergone indicating granulomatous inflammation after thorough radiographic examinations and laboratory investigations, which to our knowledge have been rarely reported by the published medical reference literature. DIGNOSES: It was initially diagnosed as lymphoma, multiple myeloma, or a metastatic disease by the radiologist. Final pathology confirmed it as an atypical form of spinal TB, which is extremely rare. INTERVENTIONS: The patient with no progressive severe neurological symptoms, spinal deformity, or a huge abscess was put on a combination of anti-TB treatment and discharged in an improved state to continue medication for a total of 12 months. OUTCOMES: This article is a case report, no outcomes. LESSONS: Multifocal extensive spinal TB involving the whole spine is rarely reported in the literature, which presents with atypical presentations and imaging features. It is noticeable that the possibility of TB is considered for any skip lesions involving the spine cautiously. Meanwhile, careful physical examination, trials of anti-TB treatment, and using the whole spine MRI routinely also play an important role in the diagnosis and treatment of this disease.

AMP-activated protein kinase stimulates osteoblast differentiation and mineralization through autophagy induction.

Previous studies have reported that adenosine monophosphate­activated protein kinase (AMPK) activation can enhance osteoblast differentiation and mineralization; however, the underlying mechanism is not fully understood. Autophagy also serves an important role in osteoblast mineralization and bone homeostasis. The present study aimed to explore whether activation of AMPK could enhance osteoblast differentiation and mineralization via the induction of autophagy. The fracture healing and nonunion animal models were established and verified by X-ray imaging. Bone maturation was measured by Masson staining and the expression of AMPK, p-AMPK, microtubule-associated proteins 1A/1B light chain 3B II, and p62 in the fracture ends were detected by immunohistochemical staining. The mRNA expression levels of alkaline phosphatase (ALP), osteocalcin ,runt-related transcription factor 2 and BCN1 were determined by reverse transcription-quantitative polymerase chain reaction. 5-Bromo-4-chloro-3-indolyl phosphate/nitro blue tetrazolium staining was used to determine ALP activity and alizarin red staining was adopted to examine mineralization. Western blot analysis was performed to detect protein expression. Autophagosome was observed by Transmission electron microscopy. Small interfering (si)RNA was used to knock down the expression of target gene. In vivo experiments demonstrated that new bone mineralization and maturation was markedly restrained in the nonunion group, alongside decreased AMPK activation and autophagic activity, compared with in the fracture healing group. The results of an in vitro study indicated that AMPK activation stimulated the osteogenic differentiation of MC3T3­E1 cells, with increases in ALP activity, mineralization, and the mRNA expression levels of ALP, osteocalcin and runt-related transcription factor 2. Furthermore, AMPK activation induced autophagy, as determined by upregulation of microtubule­associated proteins 1A/1B light chain 3B, increased autophagosome density and downregulation of p62. In addition, inhibition of autophagy reversed the effects of AMPK activation on osteoblast differentiation. These results suggested that AMPK activation may stimulate osteoblast differentiation and mineralization via the induction of autophagy, and provides evidence to suggest that enhancing AMPK activation and autophagic activity may be a potential novel approach to promote fracture healing.

miR-140-5p attenuates chemotherapeutic drug-induced cell death by regulating autophagy through inositol 1,4,5-trisphosphate kinase 2 (IP3k2) in human osteosarcoma cells.

Acquisition of drug-resistant phenotypes is often associated with chemotherapy in osteosarcoma. A number of studies have demonstrated a critical role for autophagy in osteosarcoma development, therapy and drug resistance. However, the molecular mechanisms underlying the autophagy-mediated chemotherapy resistance of osteosarcoma cells remain largely unknown. In the present study, we determined the autophagy and microRNA-140 (miR-140-5p, miRBase ID: MIMAT0000431) expression induced by chemotherapeutic drugs in osteosarcoma cells. Then we determined the promotory role of miR-140-5p to the chemotherapy-induced autophagy. Our results demonstrated that miR-140-5p expression was highly induced during chemotherapy of osteosarcoma cells, and this was accompanied by up-regulated autophagy. The increased miR-140-5p expression levels up-regulated anticancer drug-induced autophagy in osteosarcoma cells and ameliorated the anticancer drug-induced cell proliferation and viability decrease. Importantly, miR-140-5p regulates this context-specific autophagy through its target, inositol 1,4,5-trisphosphate kinase 2 (IP3k2). Therefore, the results of the present study demonstrated that miR-140-5p mediated drug-resistance in osteosarcoma cells by inducing autophagy. The present study provides evidence of miRNA regulation of autophagy through modulation of IP3 signalling. The present study recognized a novel mechanism of chemoresistance in osteosarcoma cancers.

miR-217 targeting Wnt5a in osteosarcoma functions as a potential tumor suppressor.

Osteosarcoma (OS) is the most common malignant bone tumor in children and young adults, however roles of microRNAs (miRNAs) in OS is still unclear. miR-217 is recently widely studied in various cancers, but not including OS. This study is aimed to investigate the expression and cellular function of miR-217 in OS. The data showed that miR-217 expression was consistently lower in OS tissues and cell lines than the normal controls. Restoration of miR-217 expression in MG-63 and U2OS cells could inhibit cell proliferation, migration and invasion, and induced apoptosis. Bioinformatic prediction suggested that Wnt5a is a target gene of miR-217. Using luciferase assay, mRNA and protein expression analysis, it was verified that Wnt5a was a target gene of miR-217 in OS cells. Restored expression of Wnt5a weakened miR-217-mediated suppression of tumor progression. Taken together, our data indicate that miR-217 functions as a tumor suppressor in OS by suppressing Wnt5a expression.