Enhancing the Repair of Substantial Volumetric Muscle Loss by Creating Different Levels of Blood Vessel Networks Using Pre-Vascularized Nerve Hydrogel Implants.

Volumetric muscle loss (VML), a severe muscle tissue loss from trauma or surgery, results in scarring, limited regeneration, and significant fibrosis, leading to lasting reductions in muscle mass and function. A promising approach for VML recovery involves restoring vascular and neural networks at the injury site, a process not extensively studied yet. Collagen hydrogels have been investigated as scaffolds for blood vessel formation due to their biocompatibility, but reconstructing blood vessels and guiding innervation at the injury site is still difficult. In this study, collagen hydrogels with varied densities of vessel-forming cells are implanted subcutaneously in mice, generating pre-vascularized hydrogels with diverse vessel densities (0-145 numbers/mm2) within a week. These hydrogels, after being transplanted into muscle injury sites, are assessed for muscle repair capabilities. Results showed that hydrogels with high microvessel densities, filling the wound area, effectively reconnected with host vasculature and neural networks, promoting neovascularization and muscle integration, and addressing about 63% of the VML.

Engineering large and geometrically controlled vascularized nerve tissue in collagen hydrogels to restore large-sized volumetric muscle loss.

Developing scalable vascularized and innervated tissue is a critical challenge for the successful clinical application of tissue-engineered constructs. Collagen hydrogels are extensively utilized in cell-mediated vascular network formation because of their naturally excellent biological properties. However, the substantial increase in hydrogel contraction induced by populated cells limits their long-term use. Previous studies attempted to mitigate this issue by concentrating collagen pre-polymer solutions or synthesizing covalently crosslinked collagen hydrogels. However, these methods only partially reduce hydrogel contraction while hindering blood vessel formation within the hydrogels. To address this challenge, we introduced additional support in the form of a supportive spacer to counteract the contraction forces of populated cells and prevent hydrogel contraction. This approach was found to promote cell spreading, resist hydrogel contraction, control hydrogel/tissue geometry, and even facilitate the engineering of functional blood vessels and host nerve growth in just one week. Subsequently, implanting these engineered tissues into muscle defect sites resulted in timely anastomosis with the host vasculature, leading to enhanced myogenesis, increased muscle innervation, and the restoration of injured muscle functionality. Overall, this innovative strategy expands the applicability of collagen hydrogels in fabricating large vascularized nerve tissue constructs for repairing volumetric muscle loss (∼63 %) and restoring muscle function.

Gut Mucosal Microbiome Is Perturbed in Rheumatoid Arthritis Mice and Partly Restored after TDAG8 Deficiency or Suppression by Salicylanilide Derivative.

Rheumatoid arthritis (RA), an autoimmune disease, is characterized by chronic joint inflammation and pain. We previously found that the deletion of T-cell death-associated gene 8 (TDAG8) significantly reduces disease severity and pain in RA mice. Whether it is by modulating gut microbiota remains unclear. In this study, 64 intestinal samples of feces, cecal content, and cecal mucus from the complete Freund's adjuvant-induced arthritis mouse models were compared. The α- and ß-diversity indices of the microbiome were significantly lower in RA mice. Cecal mucus showed a higher ratio of Firmicutes to Bacteroidetes in RA than healthy mice, suggesting the ratio could serve as an RA indicator. Four core genera, Eubacterium_Ventriosum, Alloprevotella, Rikenella, and Treponema, were reduced in content in both feces and mucus RA samples, and could serve microbial markers representing RA progression. TDAG8 deficiency decreased the abundance of proinflammation-related Eubacterium_Xylanophilum, Clostridia, Ruminococcus, Paraprevotella, and Rikenellaceae, which reduced local mucosal inflammation to relieve RA disease severity and pain. The pharmacological block of the TDAG8 function by a salicylanilide derivative partly restored the RA microbiome to a healthy composition. These findings provide a further understanding of specific bacteria interactions with host gut mucus in the RA model. The modulation by TDAG8 on particular bacteria can facilitate microbiota-based therapy.

Strategy for improving cell-mediated vascularized soft tissue formation in a hydrogen peroxide-triggered chemically-crosslinked hydrogel.

The physically-crosslinked collagen hydrogels can provide suitable microenvironments for cell-based functional vascular network formation due to their biodegradability, biocompatibility, and good diffusion properties. However, encapsulation of cells into collagen hydrogels results in extensive contraction and rapid degradation of hydrogels, an effect known from their utilization as a pre-vascularized graft in vivo. Various types of chemically-crosslinked collagen-based hydrogels have been successfully synthesized to decrease volume contraction, retard the degradation rate, and increase mechanical tunability. However, these hydrogels failed to form vascularized tissues with uniformly distributed microvessels in vivo. Here, the enzymatically chemically-crosslinked collagen-Phenolic hydrogel was used as a model to determine and overcome the difficulties in engineering vascular networks. Results showed that a longer duration of inflammation and excessive levels of hydrogen peroxide limited the capability for blood vessel forming cells-mediated vasculature formation in vivo. Lowering the unreacted amount of crosslinkers reduced the densities of infiltrating host myeloid cells by half on days 2-4 after implantation, but blood vessels remained at low density and were mainly located on the edge of the implanted constructs. Co-implantation of a designed spacer with cell-laden hydrogel maintained the structural integrity of the hydrogel and increased the degree of hypoxia in embedded cells. These effects resulted in a two-fold increase in the density of perfused blood vessels in the hydrogel. Results agreed with computer-based simulations. Collectively, our findings suggest that simultaneous reduction of the crosslinker-induced host immune response and increase in hypoxia in hydrogen peroxide-triggered chemically-crosslinked hydrogels can effectively improve the formation of cell-mediated functional vascular networks.

Three-dimensional semiquantitative analysis of gastric emptying SPECT.

OBJECTIVE: We used dynamic single-photon emission computed tomography (D-SPECT) to overcome the interference of the planar dynamic imaging due to the overlap of internal organs, thus more accurate physiological function can be obtained. METHODS: 3D printed gastric phantom was used to simulate gastric emptying (GE). First, the planar dynamic liquid GE procedure was used and served as the reference value; second, D-SPECT followed by repeated liquid GE procedures with three gamma cameras were used. The emptying flow rate of the gastric phantom simulated three flow rates of liquid, semisolid and solid. Third, we simulated the intestinal activity that interfered with the residual value obtained by 2D dynamic imaging, which was compared with D-SPECT. Then, we brought the 3D VOI data into the postprocessing program to obtain the residual activity curve and residual percentage. RESULTS: The residual amount obtained in the phantom at 60th minutes in the first stage is 14.57%; the residual amount of liquid emptying are Siemens: 3.33%, GE: 15.06%, PHILIPS: 1.12%; residual amount for semisolid are Siemens: 47.36%, GE: 54.25%, PHILIPS: 51.57%; residual amount for solids are Siemens: 63.98%, GE: 66.88%, PHILIPS: 63.76%. All values are within the normal range. Then, we simulated the intestinal activity that interfered with the residual value obtained by 2D dynamic imaging: 75-90 min: 10.42, 19.48, 19.51 and 11.02%; however, the residual values obtained with 3D SPECT VOI data: 75-90 min: 1.42, 1.41, 1.35 and 1.02%. These results show that the emptying data errors caused by intestinal overlap can be effectively corrected (P = 0.017). CONCLUSION: D-SPECT imaging can overcome the interference in the semiquantitative data of residual GE caused in 2D mode.

Effects of Copper on Root Morphology, Cations Accumulation, and Oxidative Stress of Grapevine Seedlings.

In the present study, a hydroponic experiment was conducted to investigate the oxidative stress and the copper (Cu) accumulation in grapevines exposed to three Cu levels (0, 5, and 15 µM) for 1, 2, and 3 days. The results showed that the root elongation was stunted at the highest-exposure concentration. The Cu accumulation in the grapevines increased with increasing Cu treatments, while the other nutrient elements (Ca, Mg and K) absorbed by the grapevines decreased. Most of the Cu taken up by the grapevines was accumulated in the roots. Compared to the data for 1 day after treatment, the Cu-addition significantly decreased the Mg and K concentration in the roots and leaves, yet increased the superoxide dismutase activity in the leaves after 3 days of treatment. For the reactive oxygen species, the malondialdehyde increased with increasing Cu levels in the roots and leaves; however, both the Cu-addition and exposure duration reduced the H2O2 level in the root. Additionally, the Cu-induced accumulation of ·O2- and H2O2 in the grapevine leaves can be observed by the histochemical staining of nitroblue tetrazolium and diaminobenzidine, respectively. In conclusion, the present results indicate that excess Cu results in a change of the root morphology and leads to oxidative stress for the grapevine leaves and roots.

A novel missense mutation of the GTP cyclohydrolase 1 gene in a Taiwanese family with dopa-responsive dystonia: A case report.

BACKGROUND: Dopa-responsive dystonia (DRD) is a clinical syndrome characterized by early onset dystonia and a dramatic response to relatively low doses of levodopa. The autosomal dominant DRD is caused by mutations in the gene coding GTP cyclohydrolase 1 (GCH1), the enzyme that catalyzes the first step in the biosynthesis of tetrahydrobiopterin. We herein report a novel gene mutation causally links to DRD. SUBJECT AND METHODS: A 23-year-old woman, presented with a history of gait abnormality and leg dystonia at age 15. Her symptoms were worsened especially in recent 2 years prior to visiting neurological clinic. In view of typical diurnal variation of dystonia, a therapeutic trial with levodopa was given and there was a dramatic response. Hence, a diagnosis of DRD was tentatively made. In addition, her father has leg dystonia since his 14 years old with leg tremor. Her 2 uncles and probably her 2 grandaunts also have limbs tremor. Genetic analysis by using PCR-direct sequencing revealed a novel point mutation (c.263G>T: p. Arg88Leu) in GCH1, including her father and asymptomatic eldest sister. CONCLUSION: We here report a Taiwanese family afflicted with DRD due to a novel missense mutation of the GCH1. The clinical features are considerably variable within the family. The findings extend the genotypic and clinical spectrum of DRD.

Lanatoside C, a cardiac glycoside, acts through protein kinase Cδ to cause apoptosis of human hepatocellular carcinoma cells.

Recent studies have revealed that cardiac glycosides, such as digitalis and digoxin, have anticancer activity and may serve as lead compounds for the development of cancer treatments. The poor prognosis of hepatocellular carcinoma (HCC) patients reflects the development of resistance to current chemotherapeutic agents, highlighting the need for discovering new small-molecule therapeutics. Here, we found that lanatoside C, an anti-arrhythmic agent extracted from Digitalis lanata, inhibited the growth of HCC cells and dramatically decreased tumor volume as well as delayed tumor growth without obvious body weight loss. Moreover, lanatoside C triggered mitochondrial membrane potential (MMP) loss, activation of caspases and translocation of apoptosis-inducing factor (AIF) into the nucleus, which suggests that lanatoside C induced apoptosis through both caspase-dependent and -independent pathways. Furthermore, we discovered that lanatoside C activated protein kinase delta (PKCδ) via Thr505 phosphorylation and subsequent membrane translocation. Inhibition of PKCδ reversed lanatoside C-induced MMP loss and apoptosis, confirming that lanatoside C caused apoptosis through PKCδ activation. We also found that the AKT/mTOR pathway was negatively regulated by lanatoside C through PKCδ activation. In conclusion, we provide the first demonstration that the anticancer effects of lanatoside C are mainly attributable to PKCδ activation.

Simultaneous cranioplasty and subdural-peritoneal shunting for contralateral symptomatic subdural hygroma following decompressive craniectomy.

BACKGROUND: Contralateral subdural hygroma caused by decompressive craniectomy tends to combine with external cerebral herniation, causing neurological deficits. MATERIAL AND METHODS: Nine patients who underwent one-stage, simultaneous cranioplasty and contralateral subdural-peritoneal shunting were included in this study. Clinical outcome was assessed by Glasgow Outcome Scale as well as Glasgow Coma Scale, muscle power scoring system, and complications. RESULTS: Postoperative computed tomography scans demonstrated completely resolved subdural hygroma and reversed midline shifts, indicating excellent outcome. Among these 9 patients, 4 patients (44%) had improved GOS following the proposed surgery. Four out of 4 patients with lethargy became alert and orientated following surgical intervention. Muscle strength improved significantly 5 months after surgery in 7 out of 7 patients with weakness. Two out of 9 patients presented with drowsiness due to hydrocephalus at an average time of 65 days after surgery. Double gradient shunting is useful to eliminate the respective hydrocephalus and contralateral subdural hygroma. CONCLUSION: The described surgical technique is effective in treating symptomatic contralateral subdural hygroma following decompressive craniectomy and is associated with an excellent structural and functional outcome. However, subdural-peritoneal shunting plus cranioplasty thoroughly resolves the subdural hygroma collection, which might deteriorate the cerebrospinal fluid circulation, leading to hydrocephalus.

Quantitative assessment of post-operative recurrence of chronic subdural haematoma using mean haematoma density.

PURPOSE: The purpose of this study was to establish a quantitative method with which to assess the post-operative recurrence of chronic subdural haematoma (CSDH). METHODS: CT scans were reviewed from 44 consecutive patients with CSDHs who underwent burr hole drainage between July 2008 and January 2012. The area of the haematoma was quantified according to the mean haematoma density (MHD) using computer-based image analysis of pre-operative brain CT scans. MHD as well as other variables of patients with and without post-operative recurrences was statistically compared. RESULTS: Post-operative recurrence was noted in six of the 44 patients that underwent surgical procedures. Among these variables, high MHD, separated type and bilateral and skull base involvement of CSDHs were shown to be significantly related to post-operative recurrence (p < 0.05). Controlling for separated type in logistic regression analysis revealed the OR of MHD as statistically significant indicators with a p value of less than 0.05 (OR = 1.243; 95% CI = 1.003-1.54). CONCLUSION: This study provides statistical proof that MHD is a significant, independent, prognostic factor for the post-operative recurrence of CSDH. As such, consideration of MHD could aid in the prediction of post-operative prognosis of CSDHs.

Effectiveness of a heel cup with an arch support insole on the standing balance of the elderly.

BACKGROUND: The use of insoles may enhance postural stability and prevent falls. The aim of this study was to design a new insole and to explore the effectiveness of the insole on the standing balance of the healthy elderly. METHODS: The study was conducted at a community hospital. Patients older than 65 years at an outpatient clinic without abnormal gait patterns, lower limb deformities, or foot pain were enrolled. The participants were assigned to good- and poor-stability groups on the basis of the stability index (SI), using the Biodex® Balance System. A heel cup with an arch support insole was provided. Participants wore the insole for 8 weeks for a minimum of 4 hours/day. A static balance test for SI was performed at the initial meeting and 8 weeks after the assigned insoles were worn for each participant. RESULTS: Five participants (10.0%) of 50 total did not finish the study. There were 25 patients in the good-stability group and 20 in the poor-stability group. The SI, before and after intervention, was significantly different for all 45 participants (3.244±0.688 versus 3.064±0.671; P<0.001). The differences in SI before and after the intervention both in the good-stability group (2.764±0.546 versus 2.592±0.538) and the poor-stability group (3.845±0.188 versus 3.655±0.128) were statistically significant (P<0.001). No statistically significant difference on changes of SI were seen between the two groups. CONCLUSION: The results suggest a heel cup with arch support insole is effective in enhancing the standing balance of the elderly. This may be of benefit in preventing falls.

Verifying three-dimensional skull model reconstruction using cranial index of symmetry.

BACKGROUND: Difficulty exists in scalp adaptation for cranioplasty with customized computer-assisted design/manufacturing (CAD/CAM) implant in situations of excessive wound tension and sub-cranioplasty dead space. To solve this clinical problem, the CAD/CAM technique should include algorithms to reconstruct a depressed contour to cover the skull defect. Satisfactory CAM-derived alloplastic implants are based on highly accurate three-dimensional (3-D) CAD modeling. Thus, it is quite important to establish a symmetrically regular CAD/CAM reconstruction prior to depressing the contour. The purpose of this study is to verify the aesthetic outcomes of CAD models with regular contours using cranial index of symmetry (CIS). MATERIALS AND METHODS: From January 2011 to June 2012, decompressive craniectomy (DC) was performed for 15 consecutive patients in our institute. 3-D CAD models of skull defects were reconstructed using commercial software. These models were checked in terms of symmetry by CIS scores. RESULTS: CIS scores of CAD reconstructions were 99.24±0.004% (range 98.47-99.84). CIS scores of these CAD models were statistically significantly greater than 95%, identical to 99.5%, but lower than 99.6% (p<0.001, p = 0.064, p = 0.021 respectively, Wilcoxon matched pairs signed rank test). These data evidenced the highly accurate symmetry of these CAD models with regular contours. CONCLUSIONS: CIS calculation is beneficial to assess aesthetic outcomes of CAD-reconstructed skulls in terms of cranial symmetry. This enables further accurate CAD models and CAM cranial implants with depressed contours, which are essential in patients with difficult scalp adaptation.

Songaricalarins A-E, cytotoxic oplopane sesquiterpenes from Ligularia songarica.

Five new highly oxygenated oplopane sesquiterpenes, songaricalarins A-E (1-5), and two known analogues (6 and 7) were isolated from the roots and rhizomes of Ligularia songarica. Their structures and configurations were elucidated by spectroscopic methods, including 2D-NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. All compounds were evaluated for in vitro cytotoxic activity against cultured A-549, MCF-7, KB, and KBVIN cells, and 4 exhibited cytotoxicity with EC50 values of 4.9, 0.8, 3.4, and 3.2 µg/mL, respectively.

DYZ-2-90, a novel neo-tanshinlactone ring-opened compound, induces ERK-mediated mitotic arrest and subsequent apoptosis by activating JNK in human colorectal cancer cells.

Over the past several decades, there has been a considerable and still growing interest in discovering natural products with anticancer potential from traditional Chinese medicine and increasing their anticancer selectivity by chemical modification. In addition, total synthesis of active compounds from natural products can overcome problems related to poor resource availability. DYZ-2-90 is a novel ring-opened compound modified from neo-tanshinlactone, which is isolated from Chinese medicinal herb tanshen. Both in vitro and in vivo tubulin polymerization assays showed that DYZ-2-90 directly bound to microtubules and rapidly induced tubulin depolymerization, inducing ERK-mediated mitotic arrest and subsequent apoptosis by JNK activation in cancer cells, respectively. These results suggest that the fate of cells that undergo mitotic arrest is dictated by two competing networks activated by DYZ-2-90: the cytoprotective ERK pathway and the stress-related JNK pathway. DYZ-2-90 is therefore a novel microtubule-destabilizing agent and a new drug candidate for cancer therapy. This paper provides a new insight into the model of mitotic cell death, which was proposed in order to elucidate how cancer cells respond to microtubule-interfering agents and prolonged cell cycle delay.

Antitumor agents. 280. Multidrug resistance-selective desmosdumotin B analogues.

6,6,8-Triethyldesmosdumotin B (2) was discovered as a MDR-selective flavonoid with significant in vitro anticancer activity against a multidrug resistant (MDR) cell line (KB-VIN) but without activity against the parent cells (KB). Additional 2 analogues were synthesized and evaluated to determine the effect of B-ring modifications on MDR-selectivity. Analogues with a B-ring Me (3) or Et (4) group had substantially increased MDR selectivity. Three new disubstituted analogues, 35, 37, and 49, also had high collateral sensitivity (CS) indices of 273, 250, and 100, respectively. Furthermore, 2-4 also displayed MDR selectivity in an MDR hepatoma-cell system. While 2-4 showed either no or very weak inhibition of cellular P-glycoprotein (P-gp) activity, they either activated or inhibited the actions of the first generation P-gp inhibitors verapamil or cyclosporin, respectively.

Kinetic process of beta-amyloid formation via membrane binding.

Recently we have studied thermodynamics of membrane-mediated beta-amyloid formation in equilibrium experiments using penetratin-lipid mixtures. The results showed that penetratin bound to the membrane interface in the alpha-helical conformation when the peptide/lipid (P/L) ratios were below a lipid-dependent critical value P/L*. When P/L reached P/L*, small beta-aggregates emerged, which served as the nuclei for large beta-aggregates. Here we studied the corresponding kinetic process to understand the potential barriers for the membrane-mediated beta-amyloid formation. We performed kinetic experiments using giant unilamellar vesicles made of 7:3 DOPC/DOPG. The observed time behavior of individual giant unilamellar vesicles, although complex, exhibited the physical effects seen in equilibrium experiments. Most interestingly, a potential barrier appeared to block penetratin from translocating across the bilayer. As a result, the kinetic value for the critical threshold P/L* is roughly one-half of the value measured in equilibrium where peptides bind symmetrically on both sides of lipid bilayers. We also investigated the similarity and differences between the charged and neutral lipids in their interactions with penetratin. We reached an important conclusion that the bound states of peptides in lipid bilayers are largely independent of the charge on the lipid headgroups.

Altaicalarins A-D, cytotoxic bisabolane sesquiterpenes from Ligularia altaica.

Four new bisabolane sesquiterpenes, altaicalarins A-D (1-4), and three known analogues (5-7) were isolated from the roots and rhizomes of Ligularia altaica. The structures were elucidated by spectroscopic methods including 2D NMR techniques, and the structure of 1 was confirmed by single-crystal X-ray diffraction. The isolated compounds were also evaluated for cytotoxic activity against human lung carcinoma (A-549), human breast adenocarcinoma (MCF-7), epidermoid carcinoma of the nasopharynx (KB), and vincristine-resistant nasopharyngeal (KBVIN) cell lines, and 1 was found to show significant cytotoxicity, with EC(50) values of 3.4, 0.8, 1.0, and 0.9 microg/mL, respectively.

Moscatilin induces apoptosis in human colorectal cancer cells: a crucial role of c-Jun NH2-terminal protein kinase activation caused by tubulin depolymerization and DNA damage.

PURPOSE: To study the effect of moscatilin (purified from the stem of orchid Dendrobrium loddigesii) on the proliferation of human colorectal cancer HCT-116 cells in vitro and in vivo. EXPERIMENTAL DESIGN: The growth inhibition of moscatilin was screened on several human cancer cell lines. The effect of moscatilin on tubulin was detected in vitro. Following moscatilin treatment on HCT-116 cells, c-Jun NH(2)-terminal protein kinase (JNK) and caspase activation was studied by Western blot analysis, and DNA damage was done by Comet assay. Specific JNK inhibitor SP600125 was cotreated to reverse moscatilin-induced apoptosis. Tumor growth inhibition of moscatilin was done on HCT-116 xenograft models. RESULTS: Moscatilin induced a time-dependent arrest of the cell cycle at G(2)-M, with an increase of cells at sub-G(1). Moscatilin inhibited tubulin polymerization, suggesting that it might bind to tubulins. Moscatilin also induced the phosphorylation of JNK1/2. SP600125 significantly inhibited the activation of caspase-9 and caspase-3 and the subsequent moscatilin-induced apoptosis. The data suggest that JNK activation may contribute to moscatilin-mediated apoptosis signaling. A parallel experiment showed that SP600125 significantly inhibits Taxol- and vincristine-induced HCT-116 cell apoptosis. This suggests that the JNK activation may be a common mechanism for tubulin-binding agents. Moreover, moscatilin induces DNA damage, phosphorylation of H2AX and p53, and up-regulation of p21. Our HCT-116 xenograft models show the in vivo efficacy of moscatilin. CONCLUSIONS: In summary, our results suggest that moscatilin induces apoptosis of colorectal HCT-116 cells via tubulin depolymerization and DNA damage stress and that this leads to the activation of JNK and mitochondria-involved intrinsic apoptosis pathway.

Denbinobin induces apoptosis by apoptosis-inducing factor releasing and DNA damage in human colorectal cancer HCT-116 cells.

Denbinobin is a phenanthraquinone derivative present in the stems of Ephemerantha lonchophylla. We showed that denbinobin induces apoptosis in human colorectal cancer cells (HCT-116) in a concentration-dependent manner. The addition of a pan-caspase inhibitor (zVAD-fmk) did not suppress the denbinobin-induced apoptotic effect, and denbinobin-induced apoptosis was not accompanied by processing of procaspase-3, -6, -7, -9, and -8. However, denbinobin triggered the translocation of the apoptosis-inducing factor (AIF) from the mitochondria into the nucleus. Small interfering RNA targeting of AIF effectively protected HCT-116 cells against denbinobin-induced apoptosis. Denbinobin treatment also caused DNA damage, activation of the p53 tumor suppressor gene, and upregulation of numerous downstream effectors (p21WAF1/CIP1, Bax, PUMA, and NOXA). A HCT-116 xenograft model demonstrated the in vivo efficacy and low toxicity of denbinobin. Taken together, our findings suggest that denbinobin induces apoptosis of human colorectal cancer HCT-116 cells via DNA damage and an AIF-mediated pathway. These results indicate that denbinobin has potential as a novel anticancer agent.