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In recent decades, the release of emerging pharmaceutical contaminants has been recognized as a challenging environmental issue. This study focuses on the adsorption of sulfamethoxazole (SMX) by pectin (Pec)-based bio-adsorbent. Pec was extracted from orange peel-waste biomass (OPB) by a microwave-assisted extraction method. Further, different concentrations of Pec from OPB (Pec-OPB); 0.5, 1, 2 and 4g were super-magnetized with Fe3O4 nanoparticles (denoted as Fe3O4@Pec-OPB(0.5g), Fe3O4@Pec-OPB(1g), Fe3O4@Pec-OPB(2g) and Fe3O4@Pec-OPB(4g), respectively). Among these synthesized bio-adsorbents, Fe3O4@Pec-OPB(1g) gave significant SMX adsorption and hence studied further in detail. Surface-morphology, structure, functional-groups, magnetic-property, and elemental-composition of facile of Fe3O4@Pec-OPB(1g) was characterized by standard analytical techniques. Different parameters for SMX adsorption on Fe3O4@Pec-OPB(1g) were investigated, such as optimal pH (4.0), kinetics (best-fitted pseudo-second-order kinetic model) and isotherm models (best-fitted Redlich-Peterson model). The maximum adsorption capacity (qm) of Fe3O4@Pec-OPB(1g) was 120 mg g−1 of SMX. Thermodynamic analysis corroborated the endothermic nature of the adsorption process. Therefore, the nano-bio-adsorbent Fe3O4@Pec-OPB(1g) exhibits excellent potential for capturing the SMX from water, suggesting that Fe3O4@Pec-OPB(1g) could be a viable option for adsorptive reclamation of hazardous cationic pollutants from water.

Biomarkers in exposure assessment are defined as the quantifiable targets that indicate the exposure to hazardous chemicals and their resulting health effect. In this study, we aimed to identify, validate, and characterize the mRNA biomarker that can detect the exposure of sodium cyanide. To identify reliable biomarkers for sodium cyanide exposure, critical criteria were defined for candidate selection: (1) the expression level of mRNA significantly changes in response to sodium thiocyanate treatment in transcriptomics results (fold change &gt, 2.0 or &lt, 0.50, adjusted p-value &lt, 0.05), and (2) the mRNA level is significantly modulated by sodium cyanide exposure in both normal human lung cells and rat lung tissue. We identified the following mRNA biomarker candidates: ADCY5, ANGPTL4, CCNG2, CD9, COL1A2, DACT3, GGCX, GRB14, H1F0, HSPA1A, MAF, MAT2A, PPP1R10, and PPP4C. The expression levels of these candidates were commonly downregulated by sodium cyanide exposure both in vitro and in vivo. We functionally characterized the biomarkers and established the impact of sodium cyanide on transcriptomic profiles using in silico approaches. Our results suggest that the biomarkers may contribute to the regulation and degradation of the extracellular matrix, leading to a negative effect on surrounding lung cells.

Benzo[a]pyrene (B[a]P) is a potentially hepatotoxic group-1 carcinogen taken up by the body through ingestion of daily foods. B[a]P is widely known to cause DNA and protein damages, which are closely related to cell transformation. Accordingly, studies on natural bioactive compounds that attenuate such chemical-induced toxicities have significant impacts on public health. This study aimed to uncover the mechanism of curcumin, the major curcuminoid in turmeric (Curcuma longa), in modulating the lipid accumulation and oxidative stress mediated by B[a]P cytotoxicity in HepG2 cells. Curcumin treatment reduced the B[a]P-induced lipid accumulation and reactive oxygen spicies (ROS) upregulation and recovered the cell viability. Cytochrome P450 family 1 subfamily A polypeptide 1 (CYP1A1) and Cytochrome P450 subfamily B polypeptide 1 (CYP1B1) downregulation resulting from decreased aryl hydrocarbon receptor (AhR) translocation into nuclei attenuated the effects of B[a]P-induced lipid accumulation and repressed cell viability, respectively. Moreover, the curcumin-induced reduction in ROS generation decreased the nuclear translocation of Nuclear factor erythroid-2-related factor 2 (Nrf2) and the expression of phase-II detoxifying enzymes. These results indicate that curcumin suppresses B[a]P-induced lipid accumulation and ROS generation which can potentially induce nonalcoholic fatty liver disease (NAFLD) and can shed a light on the detoxifying effect of curcumin.

Benzo[a]pyrene, classified as a Group 1 carcinogen, is metabolized to B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), causing DNA mutations and eventually cancer. Quercetin is a dietary flavonoid abundant in fruits and vegetables. After quercetin intake, quercetin’s metabolites isorhamnetin and miquelianin are more highly concentrated than quercetin in the human plasma. In this study, we investigated the molecular mechanisms associated with the cytoprotective effect of quercetin and its metabolites against benzo[a]pyrene from a detoxification perspective. Quercetin and its metabolite isorhamnetin reduced benzo[a]pyrene-induced cytotoxicity, whereas the metabolite miquelianin did not mitigate benzo[a]pyrene-induced cytotoxicity. Moreover, quercetin and isorhamnetin reduced intracellular levels of BPDE-DNA adducts. The formation and elimination of BPDE is mediated by the xenobiotic detoxification process. Quercetin and isorhamnetin increased the gene and protein expression levels of phase I, II, and III enzymes involved in xenobiotic detoxification. Furthermore, quercetin and isorhamnetin induced the translocation of aryl hydrocarbon receptor (AhR) and nuclear factor erythroid 2-related factor 2 (NRF2), which regulate the expression level of phase enzymes. Our results suggest that quercetin and isorhamnetin promote the metabolism, detoxification, and elimination of B[a]P, thereby increasing anti-genotoxic effects and protecting against B[a]P-induced cytotoxicity.

The utilization of waste-paper-biomass for extraction of important α-cellulose biopolymer, and modification of extracted α-cellulose for application in enzyme immobilization can be extremely vital for green circular bio-economy. Thus, in this study, α-cellulose fibers were super-magnetized (Fe3O4), grafted with chitosan (CTNs), and thiol (-SH) modified for laccase immobilization. The developed material was characterized by high-resolution transmission electron microscopy (HR-TEM), HR-TEM energy dispersive X-ray spectroscopy (HR-TEM-EDS), X-ray diffraction (XRD), vibrating sample magnetometer (VSM), X-ray photoelectron spectroscopy (XPS), and Fourier transform infrared spectroscopy (FT-IR) analyses. Laccase immobilized on α-Cellulose-Fe3O4-CTNs (α-Cellulose-Fe3O4-CTNs-Laccase) gave significant activity recovery (99.16%) and laccase loading potential (169.36 mg/g). The α-Cellulose-Fe3O4-CTNs-Laccase displayed excellent stabilities for temperature, pH, and storage time. The α-Cellulose-Fe3O4-CTNs-Laccase applied in repeated cycles shown remarkable consistency of activity retention for 10 cycles. After the 10th cycle, α-Cellulose-Fe3O4-CTNs possessed 80.65% relative activity. Furthermore, α-Cellulose-Fe3O4-CTNs-Laccase shown excellent degradation of pharmaceutical contaminant sulfamethoxazole (SMX). The SMX degradation by α-Cellulose-Fe3O4-CTNs-Laccase was found optimum at incubation time (20 h), pH (3), temperatures (30 °C), and shaking conditions (200 rpm). Finally, α-Cellulose-Fe3O4-CTNs-Laccase gave repeated degradation of SMX. Thus, this study presents a novel, waste-derived, highly capable, and super-magnetic nanocomposite for enzyme immobilization applications.

Cudrania tricuspidata has diverse biological activities, such as antioxidant, anti-inflammatory, anticancer, and neuroprotective effects. This study investigated the protective effects of C. tricuspidata fruit extracts (CTFE) against scopolamine (SCO)-induced neuron impairment. The neuroprotective effects of CTFE on SCO-induced memory dysfunction were confirmed in mice using the Barnes maze test. The results showed that co-treatment of SCO and CTFE increased the stay time in the target zone compared with SCO treatment alone. Similarly, the results obtained by the fear conditioning test revealed that SCO–CTFE co-treatment induced the freezing action time under both the contextual fear condition and the cued fear condition compared with SCO treatment alone. Moreover, we showed that CTFE reduced the SCO-induced acetylcholinesterase (AChE) activity, thereby increasing the acetylcholine concentration in mice hippocampal tissues. Consistent with the improvement of memory and recognition function in vivo, our in vitro results showed that CTFE induced cAMP response element binding protein (CREB) and extracellular regulated kinase 1/2 (ERK1/2) activity in PC12 cells and reduced SCO-induced AChE activity. In addition, the microarray results of the hippocampal tissue support our data showing that CTFE affects gene expressions associated with neurogenesis and neuronal cell differentiation markers such as spp1 and klk6. Overall, CTFE exerts a neuroprotective effect via regulation of the CREB and ERK1/2 signaling pathways and could be a therapeutic candidate for neurodegenerative diseases.

Removal of biofilms is extremely pivotal in environmental and medicinal fields. Therefore, reporting the new-enzymes and their combinations for dispersal of infectious biofilms can be extremely critical. Herein, for the first time, we accessed the enzyme &ldquo, protease from bovine pancreas type-I (PtI)&rdquo, for anti-biofilm properties. We further investigated the anti-biofilm potential of PtI in combination with &alpha, amylase from Bacillus sp. (&alpha, A). PtI showed a very significant biofilm inhibition effect (86.5%, 88.4%, and 67%) and biofilm prevention effect (66%, 64%, and 70%), against the E. coli, S. aureus, and MRSA, respectively. However, the new enzyme combination (Ec-PtI+&alpha, A) exhibited biofilm inhibition effect (78%, 90%, and 93%) and a biofilm prevention effect (44%, 51%, and 77%) against E. coli, S. aureus, and MRSA, respectively. The studied enzymes were found not to be anti-bacterial against the E. coli, S. aureus, and MRSA. In summary, the PtI exhibited significant anti-biofilm effects against S. aureus, MRSA, and E. coli. Ec-PtI+&alpha, A exhibited enhancement of the anti-biofilm effects against S. aureus and MRSA biofilms. Therefore, this study revealed that this Ec-PtI+&alpha, A enzymatic system can be extremely vital for the treatment of biofilm complications resulting from E. coli, S. aureus, and MRSA.

Hydrothermally carbonized sugarcane bagasse (SCB) has exceptional surface properties. Looking at the huge amount of SCB produced, its biocompatible nature, cheap-cost for carbonization, and its easy functionalization can give impeccable nano-biomaterials for tissue engineering applications. Herein, sugarcane bagasse was converted into hydrochar (SCB-H) by hydrothermal carbonation. The SCB-H produced was further modified with iron oxide (Fe3O4) nanoparticles (denoted as SCB-H@Fe3O4). Facile synthesized nano-bio-composites were characterized by SEM, HR-TEM, XRD, FT-IR, XPS, TGA, and VSM analysis. Bare Fe3O4 nanoparticles (NPs), SCB-H, and SCB-H@Fe3O4 were tested for cytocompatibility and osteoconduction enhancement of human adipose tissue-derived mesenchymal stem cells (hADMSCs). The results confirmed the cytocompatible and nontoxic nature of SCB-H@Fe3O4. SCB-H did not show enhancement in osteoconduction, whilst on the other hand, Fe3O4 NPs exhibited a 0.5-fold increase in the osteoconduction of hADMSCs. However, SCB-H@Fe3O4 demonstrated an excellent enhancement in osteoconduction of a 3-fold increase over the control, and a 2.5-fold increase over the bare Fe3O4 NPs. Correspondingly, the expression patterns assessment of osteoconduction marker genes (ALP, OCN, and RUNX2) confirmed the osteoconductive enhancement by SCB-H@Fe3O4. In the proposed mechanism, the surface of SCB-H@Fe3O4 might provide a unique topology, and anchoring to receptors of hADMSCs leads to accelerated osteogenesis. In conclusion, agriculture waste-derived sustainable materials like &ldquo, SCB-H@Fe3O44&rdquo, can be potentially applied in highly valued medicinal applications of stem cell differentiation.

Benzo[a]pyrene (B[a]P), a polycyclic aromatic hydrocarbon, is a group 1 carcinogen that introduces mutagenic DNA adducts into the genome. In this study, we investigated the molecular mechanisms underlying the involvement of silymarin in the reduction of DNA adduct formation by B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE), induced by B[a]P. B[a]P exhibited toxicity in HepG2 cells, whereas co-treatment of the cells with B[a]P and silymarin reduced the formation of BPDE-DNA adducts, thereby increasing cell viability. Determination of the level of major B[a]P metabolites in the treated cells showed that BPDE levels were reduced by silymarin. Nuclear factor erythroid 2-related factor 2 (Nrf2) and pregnane X receptor (PXR) were found to be involved in the activation of detoxifying genes against B[a]P-mediated toxicity. Silymarin did not increase the expression of these major transcription factors, but greatly facilitated their nuclear translocation. In this manner, treatment of HepG2 cells with silymarin modulated detoxification enzymes through NRF2 and PXR to eliminate B[a]P metabolites. Knockdown of Nrf2 abolished the preventive effect of silymarin on BPDE-DNA adduct formation, indicating that activation of the Nrf2 pathway plays a key role in preventing B[a]P-induced genotoxicity. Our results suggest that silymarin has anti-genotoxic effects, as it prevents BPDE-DNA adduct formation by modulating the Nrf2 and PXR signaling pathways.

Halloysite nanotubes (HNTs) were modified with supermagnetic Fe3O4 (M-HNTs) and functionalized with chitosan (CTA) (termed as M-HNTs–CTA). Furthermore, M-HNTs–CTA were cross-linked using glutaraldehyde and applied for covalent laccase immobilization (M-HNTs–CTA–Lac). Facile-synthesized modified HNTs were structurally characterized by scanning electron microscopy, high resolution transmission electron microscopy, X-ray photoelectron spectroscopy, and thermogravimetric analyses. M-HNTs–CTA–Lac exhibited 92.74 mg/g of laccase immobilization capacity and 92% of activity recovery. Biochemical properties of M-HNTs–CTA–Lac exhibited higher pH and temperature stabilities, with exceptional reusability capabilities until the 11th cycle. Moreover, M-HNTs–CTA–Lac exhibited 87% of 2,2′-azinobis (3-ethylbenzthiazoline-6-sulphonic acid) (ABTS)-mediated Direct Red 80 (DR80) decolorization. By the 11th cycle, M-HNTs–CTA–Lac exhibited 33% DR80 decolorization. Therefore, M-HNTs–CTA can function as CTA-modified supermagnetic nonreactors for immobilization of biomacromolecules. The investigated M-HNTs–CTA–Lac are thus biocompatible and environment-friendly biocatalysts for degradation of textile waste, such as DR80, and can be rapidly retrieved from aqueous solution by a magnet after decontamination of environmental pollutants.

Sesamol is a phenol derivative of sesame oil and a potent anti-oxidant, anti-inflammatory, anti-hepatotoxic, and anti-aging compound. We investigated the effects of sesamol on the molecular mechanisms of adipogenesis in 3T3-L1 preadipocytes. The intracellular lipid accumulation accompanied by increased extracellular release of free glycerol was decreased during differentiation on treating 3T3-L1 with sesamol. Sesamol treatment on 3T3-L1 inhibited adipogenic differentiation by down-regulating adipogenesis-related factors (C/EBPα, PPARγ, and SREBP-1). Lipid accumulation was repressed by decreasing fatty acid synthase and by up-regulating lipolysis-response genes (HSL and LPL). The molecular mechanisms of sesamol-induced inhibition in adipogenesis were mediated by increased levels of phosphorylated adenosine monophosphate-activated protein kinase and its substrate acetyl-CoA carboxylase. Sesamol treatment, in turn, modulated the different members of the mitogenactivated protein kinase family by suppressing phosphorylation of ERK 1/2 and JNK and by increasing the phosphorylation of p38. In summary, sesamol inhibits adipogenic differentiation by reducing phosphorylation levels of ERK 1/2 and JNK while inducing lipolysis by activating p38 and AMPK. Our results demonstrate that the molecular mechanisms of in vitro anti-obesity effects of sesamol are due to the combined effects of preventing both lipid accumulation and adipogenesis.

Benzo[a]pyrene (B[a]P), a group 1 carcinogen, induces mutagenic DNA adducts. Myricetin is present in many natural foods with diverse biological activities, such as anti-oxidative and anti-cancer activities. The aim of this study was to investigate the protective effects of myricetin against B[a]P-induced toxicity. Treatment of B[a]P induced cytotoxicity on HepG2 cells, whereas co-treatment of myricetin with B[a]P reduced the formation of the B[a]P-7,8-dihydrodiol-9,10-epoxide (BPDE)-DNA adduct, which recovered cell viability. Furthermore, we found a protective effect of myricetin against B[a]P-induced genotoxicity in rats, via myricetin-induced inhibition of 8-hydroxy-2&prime, deoxyguanosine (8-OHdG) and BPDE-DNA adduct formation in the liver, kidney, colon, and stomach tissue. This inhibition was more prominent in the liver than in other tissues. Correspondingly, myricetin regulated the phase I and II enzymes that inhibit B[a]P metabolism and B[a]P metabolites conjugated with DNA by reducing and inducing CYP1A1 and glutathione S-transferase (GST) expression, respectively. Taken together, this showed that myricetin attenuated B[a]P-induced genotoxicity via regulation of phase I and II enzymes. Our results suggest that myricetin is anti-genotoxic, and prevents oxidative DNA damage and BPDE-DNA adduct formation via regulation of phase I and II enzymes.

This study reports anti-bacterial assessments of ‘halloysite nanotubes (HNTs) surface-tuned with Fe3O4 and ZnO nanostructures (M-HNTs-ZnO)’ against the non-drug resistant pathogenic E. coli and S. aureus, drug-resistant methicillin-resistant S. aureus (MRSA) and their respective biofilms. Naturally occurring clay mineral the halloysite nanotubes (HNTs) are emerging materials in nano-bio-medicines. Fabricating HNTs' tunable surface with anti-bacterial nanomaterials can be a significant application in combating the deadly bacterial infections. SEM, TEM, FT-IR, XPS and VSM analysis corroborated a successful synthesis of M-HNTs-ZnO. The acquired results established the significant anti-bacterial potential of M-HNTs-ZnO against the E. coli, S. aureus and MRSA, respectively. The stepwise modifications made on HNTs enhanced anti-bacterial performance. Detailed SEM image analysis established possible anti-bacterial mechanisms. M-HNTs-ZnO found effective against the successfully established biofilms of S. aureus. The M-HNTs-ZnO applied in repeated anti-bacterial performance against E. coli, S. aureus and MRSA, marked its importance for water-treatments. In conclusion, M-HNTs-ZnO showed significant anti-bacterial properties that can be used in the treatment of infectious diseases. Also, its repeated anti-bacterial capabilities might be applied in water disinfection protocols.

Owing to the ubiquitous availability and simple biocatalysis, the anti-proliferative laccase holds enormous opportunities for anti-cancer applications. However, accessing efficient and specific (super-magnetically targetable) new delivery system for anti-proliferative laccase is vital step towards laccase based anti-cancer approach. Therefore, in this investigation, super-magnetized (Fe3O4) and chitosan (CS) functionalized halloysite nanotubes (HNTs) (termed as Fe3O4-HNTs-CS) was facile synthesized. Further, laccase from Trametes versicolor was immobilized on Fe3O4-HNTs-CS (termed as Fe3O4-HNTs-CS-Lac). Then free laccase and Fe3O4-HNTs-CS-Lac were evaluated for anti-proliferative properties against cancer cell lines of liver (HepG2), lung (H460), cervix (Hela) and stomach (AGS). Laccase and Fe3O4-HNTs-CS-Lac gave significant cytotoxicity against all studied cancer cell lines. Moreover, the apoptosis analysis and FE-SEM morphology observations of cells support the anti-proliferative potential of laccase immobilized on Fe3O4-HNTs-CS. Therefore, investigated Fe3O4-HNTs-CS-Lac is natural and super-magnetic nano-biocatalyst, having the significant anti-proliferative potential and furthermore, Fe3O4-HNTs-CS can be used as efficient and specific delivery system for other anti-cancer enzymes.

Halloysite nanotubes (HNTs) are known to be the highly emerging materials in nano-medicinal applications. However, comprehensive exploitation of HNTs for the regenerative medicinal applications is still necessary to be done. Therefore, towards enhancing the osteogenic potential of human adipose tissue-derived mesenchymal stem cells (hADMSCs), this study synthesized a novel and multifunctional nanoscaffold of chitosan (CTs) functionalized supermagnetic halloysite nanotubes (M-HNTs) decorated with the calcium phosphate 2-D nanoflakes (CaP) (termed as; M-HNTs-CTs-CaP). Stepwise modified nanoscaffolds were characterized by FE-SEM, FE-SEM-EDS, FE-HR-TEM, XPS, FT-IR and VSM analyses. The hADMSCs osteogenic potential was confirmed by calcification (Alizarin Red S staining), phosphate quantification and immunocytochemistry. Nanoscaffolds; CaP, M-HNTs-CaP and M-HNTs-CTs-CaP were significantly enhanced and up-regulated osteogenic potential compared to the HNTs, M-HNTs, M-HNTs-CTs. Among the nanoscaffolds studied, M-HNTs-CTs-CaP exhibited highest osteogenesis, due to the enhanced CaP distribution on M-HNTs-CTs surface, and synergistic osteoconduction contributed from Fe3O4, chitosan and CaP. Moreover, immunocytochemistry analysis and morphologically observation showed well differentiated osteoblast on the M-HNTs-CTs-CaP surface. Therefore, M-HNTs-CTs-CaP found to have a strong osteogenic potential of hADMSCs, and might be serve as highly applicable, next generation nanoscaffold for bone tissue engineering application.

This study demonstrates a green-route-based synthesis of high-concentration suspensions of anisotropic silver nanoparticles (AgNPs) by peptone (Pep), a soluble protein hydrolysate and an abundantly used nutrient source in microbial-media. The transformation of Ag ions from solution into a high-concentration suspension of anisotropic Pep-AgNPs, at an extremely low concentration of peptone (0.02%), indicates that the present green-route synthesis method follows &ldquo, low volume high concentration nano-synthesis&rdquo, and, hence, enhances the economic significance of the process. Process optimization with different concentrations of AgNPs (1&ndash, 5 mM), NaOH solution (5&ndash, 40 mM), and peptone (0.004%&ndash, 0.12%) gave the optimized Pep-AgNPs synthesis at 3 mM of AgNO3, 20 mM of NaOH, and 0.02% of the peptone concentrations. The green-route synthesized Pep-AgNPs were structurally characterized by the TEM, XPS, FT-IR, and XRD analyses. The Pep-AgNPs against the clinically relevant bacteria Escherichia coli and Staphylococcus aureus gave significant anti-bacterial properties, with a MIC (minimum inhibitory concentration) of 100 ppm. The colony counting and morphological observation of the bacterial cell under SEM corroborated an anti-bacterial potential of the Pep-AgNPs. Therefore, Pep-AgNPs are green-route synthesized, anisotropic, and have a significant anti-bacterial potential that can be used in many relevant applications.

Human mesenchymal stem cells (hMSCs) from adult bone marrow are able to differentiate into adipocytes, osteoblasts, chondrocytes and neuronal cells. Adipocytes in bone marrow are primarily responsible for the maintenance of bone structure by maintaining cell number balance with other stromal cells. However, the number of adipocytes in the bone marrow increases with age, leading to an imbalance of the bone marrow microenvironment, which results in a disruption of bone structure. In addition, the excessive number of adipocytes in bone marrow can cause diseases, such as osteoporosis or anemia. In this study, we investigated the effect of sesamol, a major natural phenolic compound of sesame oil, on the adipogenic differentiation of hMSCs. Numerous studies have reported the anti-oxidant property of sesamol, but its effect on cell differentiation has not yet been shown. We first found that sesamol treatment during adipogenic differentiation of hMSCs reduced intracellular lipid accumulation, which was unrelated to lipolysis. Interestingly, sesamol diminished the expression of genes responsible for adipogenesis, but increased the expression of osteogenic genes. In addition, sesamol decreased the expression of genes necessary for adipocyte maturation without affecting the expression of hMSC-specific genes. Studies concerning intracellular signaling in hMSCs showed that the extracellular signal-regulated kinase 1/2 (ERK1/2) was decreased by sesamol, which was similar with the effect of an ERK1/2 inhibitor. Overall, this study demonstrates that sesamol can attenuate the adipogenic differentiation of hMSCs without affecting its characteristics through the inhibition of ERK1/2 pathway. Herein, this study reports for the first time the effect of sesamol on hMSC differentiation and suggests the possibility of using sesamol as a therapeutic agent to treat intraosseous disruption triggered by the excessive adipogenesis of hMSCs.