Yoga Therapy in Functional Dyspepsia. A Narrative Review.

Functional dyspepsia (FD) is a common upper gastrointestinal disorder, characterized by bothersome epigastric pain or burning, fullness after meals or early satiety. The precise pathophysiology remains incompletely understood but may include the role of disordered gut-brain communication leading to disturbances in gastro-duodenal physiological functioning. Even if there are several pharmacological treatment options, it is a chronic and relapsing disorder with persistent symptoms that makes its management difficult. Yoga is a fast-spreading complementary and alternative medicine (CAM) specialty, that has gained attention in the medical field for its ability to address the physical, emotional, mental and social aspects of health and disease. Various other CAM therapies are being used for FD with varying efficacy. However, apart from one research study that used yoga therapy on abdominal pain related functional gastrointestinal disorders in children which included a few FD cases as well (11.6%), no other study using yoga therapy has been done in FD as per our best knowledge. Therefore, in the present review, we have summarized the current scientific understanding of the probable effects of yoga on the pathophysiological mechanisms involved in FD (gastric motility, fundic accommodation, hypersensitivity, duodenal inflammation, psychological distress and gut-brain dysfunction). The literature suggests yoga can have a beneficial role in the management of FD. However, rigorous research and clinical trials are required to confirm the same.

Comparative evaluation of the efficacy of nicotine chewing gum and nicotine patches as nicotine replacement therapy using salivary cotinine levels as a biochemical validation measure.

Background: Nicotine replacement therapy (NRT) and habit cessation counseling are considered the mainstay treatment for high nicotine dependence smokers. However, adherence to NRT is very poor. Among the NRTs, nicotine gums and nicotine patches are the most widely available. This study mainly evaluates the efficacy of nicotine gum and nicotine patches as NRT using salivary cotinine levels as a biochemical validation measure. Materials and Methods: A cross-sectional study was conducted on 72 known smokers who were willing to receive nicotine replacement therapy for cessation of smoking habits. The sample was divided into two groups: Group 1 tobacco smokers were offered nicotine chewing gum, and group 2 tobacco smokers were offered nicotine patches. Both groups received treatment for 12 weeks. At baseline and at the end of the trial period, the saliva samples were analyzed for cotinine levels using an enzyme-linked immunosorbent assay (ELISA). The severity of smoking was assessed using the Fagerstrom Test for Nicotine Dependence (FTND). Results: The quit rate was higher in the nicotine patch group compared with the nicotine gum group. On comparison of week one vs week twelve in the nicotine group nicotine gum group showed (CI: 18.10 to 13.83) and in the patch group (CI: 7.754 to 6.56) with P < 0.001. The pre- and post-cotinine estimation was significantly reduced for nicotine patches compared with nicotine gums, and patient compliance also yielded better results for nicotine patches. Conclusion: This study depicts that nicotine patches were better adhered to in comparison with nicotine gums, and salivary cotinine level is an effective biochemical validation measure.

Potential applications of Fe3+-activated Sr9Al6O18 nanophosphors for fingerprint detection, oxidative stress, and thrombosis treatment.

This study reports on the synthesis of Fe3+-activated Sr9Al6O18 nanophosphors (SAO:Fe NPs) using a simple solution combustion process, which emits a pale green light and possesses excellent fluorescence properties. An in-situ powder dusting method was utilized to extract unique ridge features of latent fingerprints (LFPs) on various surfaces using ultra-violet 254 nm excitation. The results showed that SAO:Fe NPs possess high contrast, high sensitivity, and no background interference, enabling the observation of LFPs for longer periods. Poroscopy, which is the examination of sweat pores on the skin's papillary ridges, is important in the identification process, and the YOLOv8x program based on deep convolutional neural networks was used to study the features visible in FPs. The potential of SAO:Fe NPs to ameliorate oxidative stress and thrombosis was analyzed. The results showed that SAO:Fe NPs have antioxidant properties by scavenging 2,2-diphenylpicrylhydrazyl (DPPH) and normalized the stress markers in NaNO2-induced oxidative stress in Red Blood Cells (RBC). In addition, SAO:Fe inhibited platelet aggregation induced by adenosine diphosphate (ADP). Therefore, SAO:Fe NPs may have potential applications in advanced cardiology and forensic sciences. Overall, this study highlights the synthesis and potential applications of SAO:Fe NPs, which can enhance the sensitivity and specificity of fingerprint detection and provide insights into developing novel treatments for oxidative stress and thrombosis.

Unclonable fluorescence of MgO-ZrO2 :Tb3+ nanocomposite for versatile applications in data security, dermatoglyphics.

Latent fingerprints (LFPs) are one among the most important types of evidences at crime scenes because of the distinctiveness and tenacity of the friction ridges in fingerprints (FPs). Therefore, it is essential in forensic science to develop a reliable method to detect LFPs. Traditional detection methods still face a number of difficulties, such as limited sensitivity, low contrast, strong background, and complex processing stages. In this study, MgO-ZrO2 :Tb3+ (1-5 mol%) (MZ:Tb) nanocomposites (NCs) were prepared via a simple solution combustion (SC) method at low temperature. The photoluminescence (PL) investigation demonstrates that when excited at 379 nm, the produced NCs emits distinctive emission peaks of terbium ions (Tb3+ ). According to the photometric results, the NCs can be employed as warm light NCs and emit light in the green portion of the colour spectrum. The estimated optical band gap from diffuse reflectance spectra is found to be in the range 4.84-4.97 eV. Regardless of the type of surface being used, the optimized MgO-ZrO2 :Tb3+ (4 mol%) (MZ:4Tb) NCs has a strong ability to minimize background fluorescence interference. With high contrast LFP and I-V type of cheiloscopy, these NCs present a flexible fluorescent mark for the identification of levels 1-3 details in forensic investigation.

Pharmacoinformatic approach to identify potential phytochemicals against SARS-CoV-2 spike receptor-binding domain in native and variants of concern.

Severe acute respiratory syndrome-related coronavirus-2 (SARS-CoV-2) pathogenesis is initiated by the binding of SARS-CoV-2 spike (S) protein with the angiotensin-converting enzyme 2 receptor (ACE2R) on the host cell surface. The receptor-binding domain (RBD) of the S protein mediates the binding and is more prone to mutations resulting in the generation of different variants. Recently, molecules with the potential to inhibit the interaction of S protein with ACE2R have been of interest due to their therapeutic value. In this context, the present work was performed to identify potential RBD binders from the Indian medicinal plant's phytochemical database through virtual screening, molecular docking, and molecular dynamic simulation. Briefly, 1578 compounds filtered from 9596 phytochemicals were chosen for screening against the RBD of the native SARS-CoV-2 S protein. Based on the binding energy, the top 30 compounds were selected and re-docked individually against the native and five variants of concern (VOCs: alpha, beta, gamma, delta, and omicron) of SARS-CoV-2. Four phytochemicals, namely withanolide F, serotobenine, orobanchol, and gibberellin A51, were found to be potential RBD binders in native and all SARS-CoV-2 VOCs. Among the four, withanolide F exhibited lower binding energy (- 10.84 to - 8.56 kcal/mol) and better ligand efficiency (- 0.3 to - 0.25) against all forms of RBD and hence was subjected to a 100 ns MD simulation which confirmed its stringent binding to the RBDs in native and VOCs. The study prioritizes withanolide F as a prospective COVID-19 (Coronavirus disease) therapeutic agent based on the observations. It warrants deeper investigations into the four promising leads for understanding their precise therapeutic value.

Comparative Analysis of Electric Field Strength, Magnetic Field Strength and Power Density around the Cell Phone Towers of Varying Characteristics with a Proposed Classification Facilitating Research on Human Population.

The continuous exposure of electromagnetic field (EMF) radiation from cell phone towers may possibly have an influence on public health. Each cell phone tower is unique in terms of number of antennas and its associated attributes; thus, the radiation exposure varies from one tower to another. Hence, a standardized method for quantifying the exposure is beneficial while studying the effects of radiation on the human population residing around the cell phone towers. A mere collection of data or human samples without understanding the cell phone tower differences may show study results such as an increase or decrease in biological parameters. Those changes may not be due to the effects of EMF radiation from cell phone towers but could be due to any other cause. Therefore, a comparative study was designed with the aim of quantifying and comparing the electric field strength (EF), magnetic field strength (MF) and power density (PD) on four sides of cell phone towers with varying numbers of antennas at 50 m and 100 m. Further, an attempt was made to develop a PD-based classification for facilitating research involving human biological samples. Through convenience sampling, sixteen cell phone towers were selected. With the use of coordinates, the geographic mapping of selected towers was performed to measure the distance between the towers. Based on the number of antennas, the cell phone towers were categorized into four groups which are described as group I with 1-5 antennas, group II comprising of 6-10 antennas, group III consisting of 11-15 antennas and group IV comprised of towers clustered with more than 15 antennas. The study parameters, namely the EF, MF and PD, were recorded on all four sides of the cell phone towers at 50 m and 100 m. One-way ANOVA was performed to compare the study parameters among study groups and different sides using the Statistical Package for the Social Sciences (SPSS) version 25.0. The mean MF in Group IV was 2221.288 ± 884.885 µA/m and 1616.913 ± 745.039 µA/m at 50 m and 100 m respectively. The mean PD in Group IV at 50 m was 0.129 ± 0.094 µW/cm2 and 0.072 ± 0.061 µW/cm2 at 100 m. There was a statistically significant (p < 0.05) increase in the MF and PD at 50 m compared to 100 m among cell phone tower clusters with more than 15 antennas (Group IV). On the other hand, a non-significant increase in EF was observed at 50 m compared to 100 m in Group II and IV. The EF, MF and PD on all four sides around cell phone towers are not consistent with distance at 50 m and 100 m due to variation in the number of antennas. Accordingly, a PD-based classification was developed as low, medium and high for conducting research involving any biological sample based on quantile. The low PD corresponds to 0.001-0.029, medium to 0.03-0.099 and high to 0.1-0.355 (µW/cm2). The PD-based classification is a preferred method over the sole criteria of distance for conducting human research as it measures the true effects of EMF radiation from the cell phone towers.

COVID-19 Pandemic-Frontline Experiences and Lessons Learned From a Tertiary Care Teaching Hospital at a Suburban Location of Southeastern India.

The key challenges to any health care setup during emergency situations, such as that of the COVID-19 pandemic would be to rapidly address hospital preparedness and response tailored to the local population, societal influences, political factors within the existing infrastructure, and workforce. Second, to adopt and moderate policies, standard operating procedures (SOPs) and guidelines issued by national and international agencies, such as WHO, CDC, and the Indian Council for Medical Research (ICMR) were tailor-made to the local conditions of the hospital and community. In this publication, we have discussed the challenges and experiences in preparation and responses to the ongoing COVID-19 pandemic at a tertiary teaching hospital situated at a suburban locale in a small union territory. Puducherry is located in the South Eastern Coromandel Coast of India. The core processes, such as hospital preparedness, adoption, and amendments to SOPs based on dynamic changes in guidelines released by the central and local government, training given to health care workers, setting up the in-house diagnostic facility, surge capacity, management of supplies during the lockdown, infection prevention, and control and patient care are discussed. We have also reinforced our experiences in translating COVID-related opportunities for research and innovation in the form of awards and research proposals for the faculty and students of our institute. The lessons learned in terms of strength and limitations on the ground level of public health during this process is worth sharing as it would provide guidance in preparing the health care setups for pre- and post-pandemic.

Evaluation of cytotoxicity levels of poly vinyl ether silicone, polyether, and poly vinyl siloxane impression materials: An in vitro study.

AIM: To assess the cytotoxicity level of newly introduced poly vinyl ether silicone (PVES) compared to poly vinyl siloxane (PVS) and polyether (PE) elastomeric impression materials. SETTINGS AND DESIGN: Comparative -Invitro study design. MATERIALS AND METHODS: Mouse cell line NIH/3T3 was grown in Dulbecco's modified Eagle's medium. Samples of three elastomers were dissolved in dimethyl sulfoxide and were tested at various concentrations. Twenty-four well plates with NIH/3T3 cells with different concentrations of elastomeric solutions were incubated at 37°C. 3-(4,5-dimethylthiazol-2-yl)-2-5-diphenyltetrazolium bromide assay was performed on day 1, 3, and 7, with a time interval of 15 min, 30 min, 60 min, and 24th h to estimate the cytotoxicity for all three elastomers. STATISTICAL ANALYSIS USED: Kruskal-Wallis ANOVA test and the period effect within the subjects, repeated-measure ANOVA was done using the Greenhouse-Geisser correction method. RESULTS: The mean cell viability (survival rate) of NIH 3T3 cells at the concentrations tested was measured. A repeated-measure Kruskal-Wallis ANOVA determined the mean survival concentration on day 1, 3, and 7. PVES showed significant decrease in the survival rate on day 1 than PVS and PE, while PVS and PE had significant decrease in the survival rates of cells on day 3 and 7 which were statistically significant (P < 0.001). CONCLUSION: PVES shows early cytotoxic signs as compared to PVS and PE, and cell viability for PVS was the highest among all. When making impression with PVES and PE, it is always better to evaluate the impression and gingival sulcus carefully with magnification to prevent adverse reaction, if any material is left inadvertently for longer period of time.

ß-PVDF based electrospun nanofibers - A promising material for developing cardiac patches.

Necrosis in heart muscles can permanently hinder the natural healthy rhythm of heart pumping mechanism. The damaged muscular tissues are replaced by scar tissues and burdens the healthy muscles resulting in further attenuated functioning of heart. Since, human heart muscles cannot regenerate naturally or it has been thought so, pharmacological procedures such as using a heart assist device are followed to restore the lost function of heart. Stem cell engineering and cardiac patches offers promising prospects with their cutting edge research reports. Cardiac patches offers a viable solution as they can also function as an implant to assist in offering the mechanical support the damaged muscles were capable of. Designing cardiac patches to suit multiple functions is not only challenging but also perilous due to the target organ with which it will be interfaced. Sensor based, electrically active, miniaturized circuitry etc., poses a huge threat to the individual in whom the device/patch is implanted. In this paper, we propose a hypothesis on choosing ß-PVDF based nanocomposites as the inimitable material for designing implantable cardiac patches. ß-PVDF based nanocomposite materials is expected to exhibit piezoelectric effect and contribute to the adherence, proliferation and maturation of stem cells. Physico-chemical characterizations followed by in vitro cell line studies were performed in ought to confirm the same. The results revealed that the ß-PVDF based nanocomposite material was mechanically stable and supportive in cardiomyocyte adherence and differentiation when compared to standard non piezoelectric scaffolds (control). Hence, an implantable ß-PVDF based novel electrospun nanocomposite scaffold is hypothesized to be the hour of need in conjugation with stem cell engineering for repairing damaged heart muscles.

Water soluble and efficient amino acid Schiff base receptor for reversible fluorescence turn-on detection of Zn²âº ions: Quantum chemical calculations and detection of bacteria.

An amino acid Schiff base (R) capable of recognizing Zn(2+) ions selectively and sensitively in an aqueous medium was prepared and characterized. Upon addition of Zn(2+) ions, the receptor exhibits fluorescence intensity enhancements (~40 fold) at 460 nm (quantum yield, Φ=0.05 for R and Φ=0.18 for R-Zn(2+)) and can be detected by naked eye under UV light. The receptor can recognize the Zn(2+) (1.04×10(-8) M) selectively for other metal ions in the pH range of 7.5-11. The Zn(2+) chelation with R decreases the loss of energy through non-radiative transition and leads to fluorescence enhancement. The binding mode of the receptor with Zn(2+) was investigated by (1)H NMR titration and further validated by ESI-MS. The elemental color mapping and SEM/EDS analysis were also used to study the binding of R with Zn(2+). Density functional theory calculations were carried out to understand the binding mechanism. The receptor was applied as a microbial sensor for Escherichia coli and Staphylococcus aureus.

Sponge-derived fijianolide polyketide class: further evaluation of their structural and cytotoxicity properties.

The sponge-derived polyketide macrolides fijianolides A (1) and B (2), isolaulimalide and laulimalide, have taxol-like microtubule-stabilizing activity, and the latter exhibits potent cytotoxicity. Insight on the biogeographical and phenotypic variations of Cacospongia mycofijiensis is presented that will enable a future study of the biosynthetic pathway that produces the fijianolides. In addition to fijianolides A and B, six new fijianolides, D-I (7-12), were isolated, each with modifications to the C-20 side chain of the macrolide ring. Compounds 7-12 exhibited a range of in vitro activities against HCT-116 and MDA-MB-435 cell lines. Fijianolides 8 and 10 were shown to disrupt interphase and mitotic division, but were less potent than 2. An in vivo evaluation of 2 using tumor-bearing severe combined immuno-deficiency mice demonstrated significant inhibition of growth in HCT-116 tumors over 28 days.

A new paradigm for the development of anticancer agents from natural products.

A novel pharmacology paradigm has been developed which quickly and efficiently moves prospective anticancer drugs from the discovery phase through pharmacology testing and into therapeutic trial assessment. Following discovery, the drug is first assessed in a clonogenic assay which determines the cytotoxic effect of different concentrations of the drug at 3 different exposure durations: 2h, 24h and continuous (168 h). Second, pharmacokinetic information is obtained in both plasma and tumor for the drug administered at the maximum tolerated dose given intravenously. The first study defines the time-concentration profile required to obtain a specific cell survival for the tumor cells; the second study determines the concentration-time profile that can be obtained in both plasma and tumor at the maximum tolerated dose of the drug. The integration of this information determines whether a successful therapeutic trial is possible. Only when a drug shows therapeutic efficacy is a proteomics-based mechanism of action study initiated. Two drugs have been assessed in this paradigm: salicortin and fascaplysin A.

A comparison of drug-treated and untreated HCT-116 human colon adenocarcinoma cells using a 2-D liquid separation mapping method based upon chromatofocusing PI fractionation.

A multidimensional chromatographic 2-D liquid-phase separation method has been developed for differential display of proteins from cell lysates and applied to a comparison of protein expression between Peninsularinone-treated and untreated HCT-116 human colon adenocarcinoma cells. The method involves fractionation according to pI using chromatofocusing with analytical columns in the first dimension followed by separation of the proteins in each pI fraction using nonporous reversed-phase HPLC. A 2-D map of the protein content of each cell line based upon pI versus hydrophobicity as detected by UV absorption was generated and a differential display map indicating the presence of up- or downregulated proteins displayed using ProteoVue and DeltaVue software. Using this method, > 1000 protein bands could be detected in 0.2 pH fractions over a pH range of 4-7. In addition, the liquid eluent from the separation was directed on-line into an electrospray TOF-MS to obtain an accurate molecular weight of the intact proteins. An accurate molecular weight together with the peptide map was used to obtain protein identification using database searching. The method has been shown to have high reproducibility for quantitative differential display analysis of interlysate comparisons, generation of accurate protein identifications, and ease of data interpretation. It has been used herein to identify proteins that change as a function of drug treatment. The relative simplicity of the current procedure and the potential for full automation will make this technique an essential tool in future proteomic studies.

Cellular drug action profile paradigm applied to XK469.

The cellular paradigm presented here defines the cellular action profile of new anticancer agents that complements our discovery and development paradigm. The main elements of this profile include a concentration clonogenicity response relationship on proliferating and plateau phase cells, flow cytometry studies assessing progression delay and apoptosis, macromolecular synthesis inhibition, and DNA damage assessment by the comet assay; other specific assessments then derive from these findings such as topoisomerase assays. XK469 is a new anticancer agent derived from the herbicide Assure that is the inactive parent compound of a family of quinoxaline analogs found to have anticancer activity in vivo. We have applied the described cellular action profile paradigm to XK469 to define a novel action at the cellular level. XK469 is a G2M phase-specific, antiproliferative agent whose activity is related to the 7-position of the chlorine ion in the benzene ring and expressed through a unique cellular action profile resulting in the irreversible increase in cyclin B1 (possibly by specific inhibition of its ubiquitination) and leading, in the absence of apoptosis, to the final mitotic arrest of HCT-116 cells in prophase with subsequent loss of clonogenicity.

Inhibition of macromolecular synthesis by cryptophycin-52.

Cryptophycin (CP)-52, a synthetic analog of CP-1, possesses potent and selective antiproliferative activity against human solid tumors both and. Based on an algorithm developed in this laboratory using HCT-116 human colon adenocarcinoma cells, CP-52 exhibited a time- and concentration-dependent antiproliferative effect in the clonogenic assay. Inhibition of both DNA and RNA synthesis was observed in the absence of any effect on protein synthesis following a 24-h exposure to CP-52, at a time when proliferating cells were arrested in the G2/M phase of the cell cycle. In summary, we interpret these data to indicate that the selective inhibition of DNA synthesis may be a major causative factor responsible for the antiproliferative activity of CP-52 and subsequent G2/M arrest.

XK469, a novel antitumor agent, inhibits signaling by the MEK/MAPK signaling pathway.

PURPOSE: XK469 (NSC 697887) is a novel antitumor agent with broad activity against a variety of tumors including drug-resistant tumors. Previous studies have indicated that XK469 is an antiproliferative agent with a low cytotoxic effect in human H116 tumor cells. In this study, we sought to determine the signaling pathways involved in mediating its antiproliferative activity. METHODS: The antiproliferative activity of XK469 was tested using human U-937 leukemia cells in culture. XK469-induced cell cycle arrest was determined using flow cytometric analysis. Phosphorylation/activation of MEK and MAPK was analyzed using immunoblot analyses with specific antibodies against p-MEK and p-MAPK. RESULTS: Cell cycle analysis revealed that XK469 arrested U-937 cells at the G(2)/M phase. Compared with conventional anticancer agents, XK469 showed very low, if any, cytotoxic or proapoptotic effect against U-937 cells. In contrast, treatment of U-937 cells with vinblastine, doxorubicin and m-AMSA resulted in extensive cell death through apoptotic pathways. XK469, but not other agents, potently inhibited the phosphorylation/activation of MEK in U-937 cells cultured in serum-containing medium. XK469 was also able to block the activation of MEK by serum addition in starved U-937 cells. Exposure of cells to XK469 for 1 h was sufficient to inhibit the activation of MEK and its downstream kinase, MAPK. The antiproliferative response to XK469 was correlated with a steady accumulation of cyclins B1 and A, which appeared to be a direct result of G(2)/M arrest. CONCLUSIONS: Our findings suggest that the antiproliferative effect of XK469 is mediated by inhibiting the MEK/MAPK signaling pathways in U-937 human leukemia cells.

Mitotic arrest induced by XK469, a novel antitumor agent, is correlated with the inhibition of cyclin B1 ubiquitination.

XK469 (NSC 697887) is a novel antitumor agent with broad activity against a variety of tumors. Previous studies suggest that XK469 is a topoisomerase II beta poison with functional activity similar to that of 4'-(9-acridinylamino) methanesulfon-m-anisidide (m-AMSA). The goal of our study was to investigate its mechanism of action further using a human HCT-116 (H116) colon tumor cell model. Concentration-survival curves with continuous exposure indicated that XK469 had low cytotoxic activity against H116 cells. Cell cycle analysis revealed that XK469 is a phase-specific cell cycle blocker that is associated with increased levels of cyclin B1, cyclin A and p53 but not CDK1 (cdc2) or cyclin E. In contrast, treatment of H116 cells with m-AMSA caused a total degradation of both cyclin A and B1 but enhanced expression of cyclin E and p53. Accumulation of cyclin B1 in XK469-treated cells was correlated with the inhibition of cyclin B1 ubiquitination, a metabolic process mandatory for proteasome-mediated protein turnover. However, no inhibition of cyclin B1 ubiquitination was detected in cells treated with m-AMSA or colchicine, a known mitotic inhibitor. Furthermore, unlike m-AMSA, XK469 did not induce caspase activation or apoptotic cell death in H116 cells. Our results suggest that XK469 is a phase-specific cell cycle inhibitor with a unique mechanism of action that is correlated with the inhibition of cyclin B1 ubiquitination and its accumulation at early M phase.

Painting with a molecular brush: genomic/proteomic interfacing to define the drug action profile of novel solid-tumor selective anticancer agents.

XK469 is an investigational anticancer agent that exhibits antiproliferative activity in tumor-bearing animal models. We examined the drug-action profile of this agent at the molecular level regarding alterations induced in gene expression and proteins in HCT-116 human colon adenocarcinoma cells. We used a unique cDNA microarray (GeneMap(TM) Cancerarray) comprising 1152 human tumor-related genes and 2-D gel electrophoresis, respectively, following a 24-hour exposure to a drug concentration that killed a two-log fraction of HCT-116 clonogenic cells. Functional gene cluster profile (FGCP) analysis of the 71 out of 1152 genes that displayed a >2-fold increase or decrease in expression (over untreated control) identified a drug-specific involvement of the MAPK signal transduction pathway. MAPK signaling together with the involvement of ubiquitin proteins from 2-D gel electrophoresis suggest a novel drug-action profile at the molecular level for the in vitro antiproliferative activity of XK469.